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Aetna Aetna
Clinical Policy Bulletin:
Adoptive Immunotherapy and Cellular Therapy
Number: 0641


Policy

Aetna considers adoptive immunotherapy, using either tumor-infiltrating lymphocytes (TILs) or lymphokine-activated killer (LAK) cells that are activated in-vitro by interleukin-2 (IL-2), experimental and investigational for the treatment of the following indications (not an all-inclusive list) due to lack of adequate evidence that it is more beneficial than IL-2 alone:

  • Alzheimer disease and other amyloid disorders
  • Breast cancer
  • Esophageal cancer
  • Head and neck cancer
  • Hepato-cellular carcinoma
  • Intractable viral diseases and other infectious diseases
  • Lung cancer (inclduing non-small cell lung cancer)
  • Malignant glioma
  • Melanoma
  • Myeloma
  • Ovarian cancer
  • Pancreatic cancer
  • Renal cell carcinoma
  • Sporadic inclusion-body myositis
  • Other malignancies

Aetna consider cellular therapy (also known as cell therapy, embryonic cell therapy, fresh cell therapy, live cell therapy, glandular therapy, organotherapy, and xenotransplant therapy) experimental and investigational for the treatment of the following indications (not an all-inclusive list) due to lack of adequate evidence:

  • Acquired immune deficiency syndrome
  • Athritis
  • Asthma
  • Cancer
  • Chronic fatigue
  • Colonic diverticulum
  • Diabetes
  • Hypertension.

See also CPB 0377 - Dendritic Cell Immunotherapy, and CPB 0638 - Donor Lymphocyte Infusion.



Background

Adoptive Immunotherapy:

Adoptive immunotherapy involves removing lymphocytes from the patient, boosting their anti-cancer activity, growing them in large numbers, and then returning them to the patient:

Lymphokine-activated killer (LAK) cells: Initial experiments in adoptive immunotherapy involved removing lymphocytes from the blood of a patient and growing them in the presence of the lymphokine interleukin-2 (IL-2), an immune stimulator.  The cells were then returned to the patient.  These lymphocytes were called LAK cells.

Tumor-infiltrating lymphocytes (TILs): A stronger response against tumor cells is obtained using lymphocytes isolated from the tumor itself.  These tumor-infiltrating lymphocytes are grown in the presence of IL-2 and returned to the body to attack the tumor.  Researchers are also using radiolabeled monoclonal antibodies for tumor antigens to even more closely identify lymphocytes specific for tumor cells.

Adoptive immunotherapy and dendritic cell immunotherapy are forms of cellular therapy, where ex-vivo processed cells are introduced into the body.  Adoptive immunotherapy uses immune effector cells (e.g., T cells), whereas dendritic cell immunotherapy uses antigen-presenting cells.

Pre-clinical studies suggested anti-tumor activity could be enhanced by using IL-2 together with ex-vivo activated and expanded autologous lymphocytes.  Also, the first objective responses with high-dose bolus IL-2 therapy were noted in patients receiving IL-2 together with LAK cells prepared through in-vitro activation of autologous peripheral blood lymphocytes that were harvested by lymphopheresis, and initially, it appeared that the combination of IL-2/LAK was more active than IL-2 alone.

Clinical studies have failed to demonstrate that the addition of activated LAK cells with IL-2 is any more effective than IL-2 alone.  Major IL-2/LAK clinical trials in patients with renal cell carcinoma have been conducted by several groups, including the National Cancer Institute (NCI) Surgery Branch, the Interleukin-2/LAK Working Group, and the NCI-sponsored Modified Group C centers.  A subset of the NCI Surgery Branch's patients with renal cell carcinoma and with all patients entered into the Modified Group C trials were randomized to receive IL-2 alone or together with LAK cells.  Response rates to IL-2 used alone and together with LAK cells as well as durability of responses did not differ substantially.  In a review of the literature, Grimm (2000) concluded that “the data do not support a major contribution of ex vivo activated and adoptively transferred LAK cells to the efficacy of high-dose bolus IL-2 in patients with renal cell carcinoma.”

Similar conclusions were reached regarding the adoptive transfer of LAK cells in patients with melanoma treated with high-dose bolus IL-2.  Response rates with IL-2/LAK are not different from those observed with high-dose IL-2 alone, and IL-2/LAK therapy in other solid tumors has been disappointing.  While attempts to generate LAK at the tumor site remain attractive, Grimm (2000) concluded that the intravenous infusion of LAK is not likely to prove effective in cases beyond the blood-borne metastatic deposits, which appear just as sensitive to interleukin alone.

Grimm (2000) noted that clinical trials conducted with IL-2 and TIL has also been disappointing.  Clinical trials of IL-2/TIL have been performed on the basis of the theory that TIL would include those with tumor specific activity, which was somehow suppressed in the vicinity of the tumor.  These lymphocytes are produced by placing digested, fresh tumor biopsies into an in-vitro culture with IL-2.  Although some early studies have noted response rates using TIL cells together with IL-2 in the 30 to 40 % range, there are no studies comparing responses with TIL cells compared with IL-2 alone.

A Cochrane meta-analysis examined the published evidence for adoptive immunotherapy in renal cell cancer (Coppin et al, 2004).  The investigators identified 1 study that compared high dose IL-2 plus LAK cells with high dose IL-2 alone (Rosenberg et al, 1993).  Three other studies examined IL-2 given in modified schedules to reduce toxicity but with additions intended to maintain or improve efficacy compared to the high dose IL-2 regimen.  The modifiers included TILs (Figlin et al, 1999), or LAK cells (McCabe et al, 1991; Law et al, 1995).  The investigators found that examination of individual and pooled response rates showed no clear evidence of enhancement for remission (Peto OR 0.93, 95 % confidence interval [CI]: 0.50 to 1.74) (Coppin et al, 2004).  Likewise for the 3 studies reporting survival, 1-year mortality was not reduced (Peto OR 0.78, 95 % CI: 0.50 to 1.21).

In a phase II clinical study, Kimura and associates (2008) evaluated the effectiveness and toxicity of adjuvant chemo-immunotherapy using dendritic cells and activated killer cells are in post-surgical primary lung cancer patients (n = 31).  The activated killer cells and dendritic cells (AKT-DC) obtained from tissue cultures of tumor-draining lymph nodes (TDLN) or from TDLN co-cultured with peripheral blood lymphocytes (TDLN-Pb) were used for the adoptive transfer of immunotherapy.  Patients received 4 courses of chemotherapy along with immunotherapy every 2 months for 2 years.  Three cases were excluded because of refusal by the patients after 1 to 2 courses of immunotherapy.  For the 28 cases treated, a total of 313 courses of immunotherapy were administered.  The main toxicities were fever (78.0 %), chill (83.4 %), fatigue (23.0 %) and nausea (17.0 %) on the day of cell transfer.  The 2- and 5-year survival rates were 88.9 % (95 % CI: 95.9 to 81.9) and 52.9 % (95 % CI: 76.4 to 29.4).  The authors concluded that adoptive transfer of activated killer cells and dendritic cells from the tumor-draining lymph nodes of primary lung cancer patients is feasible and safe, and a large-scale multi-institutional study is needed for assessing the effectiveness of this treatment.

Bernhard and colleagues (2008) stated that the human epidermal growth factor receptor 2 (HER2) has been targeted as a breast cancer-associated antigen by immuno-therapeutical approaches based on HER2-directed monoclonal antibodies and cancer vaccines.  These investigators described the adoptive transfer of autologous HER2-specific T-lymphocyte clones to a patient with metastatic HER2 over-expressing breast cancer.  The HLA/multimer-based monitoring of the transferred T lymphocytes revealed that the T cells rapidly disappeared from the peripheral blood.  The imaging studies indicated that the T cells accumulated in the bone marrow (BM) and migrated to the liver, but were unable to penetrate into the solid metastases.  The disseminated tumor cells in the BM disappeared after the completion of adoptive T-cell therapy.  The findings of this study suggest the therapeutic potential for HER2-specific T cells for eliminating disseminated HER2-positive tumor cells and propose the combination of T cell-based therapies with strategies targeting the tumor stroma to improve T-cell infiltration into solid tumors.

Rolle and colleagues (2010) noted that glioblastoma multiforme (GBM) is the most common and lethal primary malignant brain tumor.  The traditional treatments for GBM, including surgery, radiation, and chemotherapy, only modestly improve patient survival.  Therefore, immunotherapy has emerged as a novel therapeutic modality.  Current immunotherapeutic approaches for glioma can be divided into 3 categories: (i) immune priming (active immunotherapy), (ii) immunomodulation (passive immunotherapy), and (iii) adoptive immunotherapy.

Chekmasova and Brentjens (2010) stated that adoptive transfer of genetically modified autologous tumor-reactive T cells is a promising novel anti-tumor therapy for many cancers.  Ovarian carcinomas in particular appear to be suited to this therapeutic approach based on the fact that these tumors are relatively immunogenic, inducing an endogenous T cell response.  Furthermore, the degree to which this endogenous T cell- mediated immune response is evident correlates to long-term patient prognosis following surgery and chemotherapy.  To this end, adoptive T cell immunotherapy strategies for the treatment of ovarian carcinomas appear to be particularly promising and are currently being investigated at several centers in both pre-clinical and clinical settings.

Adoptive immunotherapy is also being studied as a means for treating non-malignant conditions such as amyloid disorders (e.g., Alzheimer disease, sporadic inclusion-body myositis) and infectious diseases/intractable viral diseases.  However, there is currently insufficient evidence to support the clinical value of these potential applications of adoptive immunotherapy.

Yamasaki et al (2011) noted that Vα24 natural killer T (NKT) cells have potent anti-tumor activity.  These researchers performed a phase II clinical study in patients with head and neck squamous cell carcinoma (HNSCC) using ex-vivo expanded Vα24 NKT cells and α-galactosylceramide (αGalCer; KRN7000)-pulsed antigen-presenting cells (APCs) to investigate the efficacy and induction of NKT cell-specific immune responses.  The subjects were 10 patients with locally recurrent and operable HNSCC.  One course of nasal submucosal administration of αGalCer-pulsed APCs and intra-arterial infusion of activated NKT cells via tumor-feeding arteries was given before salvage surgery.  Anti-tumor effects, NKT cell-specific immune responses in extirpated cancer tissue and peripheral blood, safety, and pathological effects were evaluated.  Five cases achieved objective tumor regression.  The number of NKT cells increased in cancer tissues in 7 cases and was associated with tumor regression.  The combination therapy induced NKT cell-specific immune responses in cancer tissues that were associated with beneficial clinical effects.

Kurusaki et al (2011) stated that APCs play a crucial role in the induction of immune responses.  However, the optimal administration route of tumor-specific APCs for inducing effective immunological responses via cancer immunotherapy remains to be elucidated.  Human NKT cells are known to have strong anti-tumor activities and are activated by the specific ligand, namely, αGalCer. A total of 17 patients with HNSCC were enrolled in this study.  Patients received an injection of αGalCer-pulsed APCs into the nasal, or the oral floor submucosa.  Then total body image and single photon emission computed tomography (SPECT) images were examined.  The immunological responses including the number of peripheral blood NKT cells, anti-tumor activities and the CD4(+) CD25(high) Foxp3(+) T cells (Tregs) induced following APCs were also compared.  APCs injected into the nasal submucosa quickly migrated to the lateral lymph nodes and those injected into the oral floor submucosa dominantly migrated to the submandibular nodes rather than the lateral lymph nodes.  An increase in the absolute number of NKT cells and the IFN-γ producing cells was observed in peripheral blood after injection of the APCs into the nasal submucosa, however, these anti-tumor activities were not detected and the increased frequency of Treg cells were observed after administration into oral floor.  The authors concluded that these findings indicated that a different administration route of APCs has the potential to bring a different immunological reaction.  The submucosal administration of αGalCer into the oral submucosa tends to induce immunological suppression.

In a phase I/II 2-arm trial (Rapoport et al, 2011), a total of 54 patients with myeloma received autografts followed by ex vivo anti-CD3/anti-CD28 co-stimulated autologous T cells at day 2 after transplantation. Study patients positive for human leukocyte antigen A2 (arm A, n = 28) also received pneumococcal conjugate vaccine immunizations before and after transplantation and a multi-peptide tumor antigen vaccine derived from the human telomerase reverse transcriptase and the anti-apoptotic protein survivin.  Patients negative for human leukocyte antigen A2 (arm B, n = 26) received the pneumococcal conjugate vaccine only.  Patients exhibited robust T-cell recoveries by day 14 with supra-physiologic T-cell counts accompanied by a sustained reduction in regulatory T cells.  The median event-free survival (EFS) for all patients is 20 months (95 % CI: 14.6 to 24.7 months); the projected 3-year overall survival is 83 %.  A subset of patients in arm A (36 %) developed immune responses to the tumor antigen vaccine by tetramer assays, but this cohort did not exhibit better EFS.  Higher post-transplantation CD4(+) T-cell counts and a lower percentage of FOXP3(+) T cells were associated with improved EFS.  Patients exhibited accelerated polyclonal immunoglobulin recovery compared with patients without T-cell transfers.  Adoptive transfer of tumor antigen vaccine-primed and costimulated T cells leads to augmented and accelerated cellular and humoral immune reconstitution, including anti-tumor immunity, after autologous stem cell transplantation for myeloma.

In a phase II clinical trial, Geller et al (2010) evaluated the tumor response and in-vivo expansion of allogeneic natural killer (NK) cells in recurrent ovarian and breast cancer.  Patients underwent a lympho-depleting preparative regimen: fludarabine 25 mg/m(2) × 5 doses, cyclophosphamide 60 mg/kg × 2 doses, and, in 7 patients, 200 cGy total body irradiation (TBI) to increase host immune suppression.  An NK cell product, from a haplo-identical related donor, was incubated over-night in 1,000 U/ml IL-2 prior to infusion.  Subcutaneous IL-2 (10 MU) was given 3 times/week × 6 doses after NK cell infusion to promote expansion, defined as detection of greater than or equal to 100 donor-derived NK cells/μL blood 14 days after infusion, based on molecular chimerism and flow cytometry.  A total of 20 patients (14 ovarian cancer, 6 breast cancer) were enrolled.  The median age was 52 (range of 30 to 65) years.  Mean NK cell dose was 2.16 × 10(7)cells/kg.  Donor DNA was detected 7 days after NK cell infusion in 9/13 (69 %) patients without TBI and 6/7 (85 %) with TBI.  T-regulatory cells (Treg) were elevated at day +14 compared with pre-chemotherapy (p = 0.03).  Serum IL-15 levels increased after the preparative regimen (p < 0.001).  Patients receiving TBI had delayed hematologic recovery (p = 0.014).  One patient who was not evaluable had successful in-vivo NK cell expansion.  The authors concluded that adoptive transfer of haplo-identical NK cells after lympho-depleting chemotherapy is associated with transient donor chimerism and may be limited by reconstituting recipient Treg cells.  They stated that strategies to augment in-vivo NK cell persistence and expansion are needed.

Weber et al (2011) noted that adoptive T-cell therapy (ACT) using expanded autologous tumor-infiltrating lymphocytes (TIL) and tumor antigen-specific T cell expanded from peripheral blood are complex but powerful immunotherapies directed against metastatic melanoma.  A number of non-randomized clinical trials using TIL combined with high-dose IL-2 have consistently found clinical response rates of 50 % or more in metastatic melanoma patients accompanied by long progression-free survival.  Recent studies have also established practical methods for the expansion of TIL from melanoma tumors with high success rates.  These results have set the stage for randomized phase II/III clinical trials to determine whether ACT provides benefit in stage IV melanoma.  These investigators provided an overview of the current state-of-the art in T-cell-based therapies for melanoma focusing on ACT using expanded TIL and address some of the key unanswered biological and clinical questions in the field.  Different phase II/III randomized clinical trial scenarios comparing the efficacy of TIL therapy to high-dose IL-2 alone were described.  Finally, the authors provided a roadmap describing the critical steps required to test TIL therapy in a randomized multi-center setting.  They suggested an approach using centralized cell expansion facilities that will receive specimens and ship expanded TIL infusion products to participating centers to ensure maximal yield and product consistency.  If successful, this approach will definitively answer the question of whether ACT can enter mainstream treatment for cancer.

Cellular Therapy:

Barrett (2008) stated that cellular therapy (also known as embryonic cell therapy, fresh cell therapy, glandular therapy, live cell therapy, and organotherapy) refers to various procedures in which processed tissue from animal embryos, fetuses or organs, is injected or taken orally.  Products are obtained from specific organs or tissues said to correspond with the unhealthy organs or tissues of the recipient.  Proponents of cellular therapy claim that the recipient's body automatically transports the injected cells to the target organs, where they supposedly strengthen them and regenerate their structure.  The organs and glands used in cell treatment include adrenals, brain, heart, kidney, liver, ovary, pancreas, parotid, pituitary, spleen, testis, thymus, and thyroid.  Several different types of cell or cell extract can be given simultaneously -- some practitioners routinely give up to 20 or more at once.  The author noted that the theory behind cellular therapy is senseless; and the American Cancer Society (ACS) has strongly advised people not to seek it.

According to the American Cancer Society (ACS, 2008), cell therapy (also known as cellular therapy, fresh cell therapy, live cell therapy, glandular therapy, and xenotransplant therapy) entails the injection of processed tissue from the organs, embryos, or fetuses of animals (e.g., cows or sheep).  This approach is supposed to repair cellular damage and heal sick or failing organs.  Cell therapy is promoted as an alternative therapy for cancer, arthritis, heart disease, Down syndrome, and Parkinson disease.   It is also marketed to counter the effects of aging, reverse degenerative diseases, improve general health, increase vitality and stamina, and enhance sexual function.  Some practitioners have proposed using cell therapy to treat AIDS patients.  However, available scientific evidence does not support claims that cell therapy is effective in treating cancer or any other disease.  Moreover, serious adverse reactions can result from cell therapy.

Furthermore, the Centers for Medicare and Medicaid Services states that cellular therapy involves the practice of injecting humans with foreign proteins like the placenta or lungs of unborn lambs.  Cellular therapy is without scientific or statistical evidence to document its therapeutic efficacy and, in fact, is considered a potentially dangerous practice.  Accordingly, cellular therapy is not considered reasonable and necessary.

 
CPT Codes / HCPCS Codes / ICD-9 Codes
Adoptive Immunotherapy:
Other CPT codes related to the CPB:
36511
86357
88230
88237
88239
HCPCS code not covered for indications listed in the CPB:
S2107 Adoptive immunotherapy i.e., development of specific anti-tumor reactivity (e.g., tumor-infiltrating lymphocyte therapy) per course of treatment
ICD-9 codes not covered for indications listed in the CPB (not all-inclusive):
001.0 - 139.8 Infectious and parasitic diseases
140.0 - 208.91, 209.00 - 209.30, 230.0 - 234.9 Malignant neoplasm and malignant carcinoid tumors
277.30 - 277.39 Amyloidosis
331.0 Alzheimer's disease
359.71 Inclusion body myositis
Cellular Therapy:
HCPCS codes not covered for indications listed in the CPB:
M0075 Cellular therapy
ICD-9 codes not covered for indications listed in the CPB (not all inclusive):
042 Human immunodeficiency virus [HIV] disease
140.0 - 208.91, 209.00 - 209.30, 230.0 - 234.9 Malignant neoplasm and malignant carcinoid tumors
250.00 - 250.93 Diabetes mellitus
401.0 - 405.99 Hypertensive disease
493.00 - 493.92 Asthma
562.10 - 562.13 Diverticula of colon
710.0 - 719.99 Arthropathies and related disorders
780.71 Chronic fatigue syndrome


The above policy is based on the following references:

Adoptive Immunotherapy:

  1. Ward DE. Immunotherapy and cancer vaccines. In: The Cancer Handbook. A Guide for the Nonspecialist. The Ohio State University Comprehensive Cancer Center-Arthur G. James Cancer Hospital and Research Institute. Columbus, OH: Ohio State University Press; 1996. Available at: http://www.acs.ohio-state.edu/units/cancer/handbook/immuno.pdf. Accessed July 1, 2002.
  2. Grimm EA. Cytokines: Biology and applications in cancer medicine. In: Cancer Medicine. 5th ed. Ch. 63. RC Bast, DW Kufe, RE Pollock, eds. Hamilton, ON: BC Decker, Inc.; 2000.
  3. Rosenberg SA, Lotze MT, Yang JC, et al. Prospective randomized trial of high-dose interleukin-2 alone or in conjunction with lymphokine-activated killer cells for the treatment of patients with advanced cancer. J Natl Cancer Inst. 1993;85(8):622-632.
  4. Rosenberg SA. Karnofsky Memorial Lecture: The immunotherapy and gene therapy of cancer. J Clin Oncol. 1992;10:180-199.
  5. Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: Analysis of 270 patients treated between 1985 and 1993. J Clin Oncol. 1999;17(7):2105-2116.
  6. Benyunes MC, Fefer A. IL-2 in the treatment of hematologic malignancies. In: Therapeutic Applications of Interleukin. MB Atkins, JW Mier, eds. New York, NY: Marcel Dekker; 1993:163-175.
  7. Sznol M, Hawkins MJ. Interleukin-2 in malignancies other than melanoma and renal cell carcinoma. In: Therapeutic Applications of Interleukin. MB Atkins, JW Mier, eds. New York, NY: Marcel Dekker; 1993:177.
  8. Weiss GR, Margolin KA, Aronson FR, et al. A randomized phase II trial of continuous infusion interleukin-2 or bolus injection interleukin-2 plus lymphokine-activated killer cells for advanced renal cell carcinoma. J Clin Oncol. 1992;10(2):275-281.
  9. Rosenberg SA, Packard BS, Aebersold PM, et al. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988;319(25):1676-1680.
  10. Margolin KA, Rayner AA, Hawkins MJ, et al. Interleukin-2 and lymphokine-activated killer cell therapy of solid tumors: Analysis of toxicity and management guidelines. J Clin Oncol. 1989;7(4):486-498.
  11. McCabe MS, Stablein D, Hawkins MJ. The Modified Group C experience - Phase III randomized trials of IL-2 vs IL-2 + LAK in advanced renal cell carcinoma and advanced melanoma [abstract]. Proceedings of the Annual Meeting of the American Society of Clinical Oncology. 1991;10:A714.
  12. 1991;10:A714.Hoffman DM, Gitlitz BJ, Belldegrun A, et al. Adoptive cellular therapy. Semin Oncol. 2000;27(2):221-233.
  13. Wallack MK, Sivanandham M, Balch CM, et al. Surgical adjuvant active specific immunotherapy for patients with stage III melanoma: The final analysis of data from a phase III, randomized, double-blind, multicenter vaccinia melanoma oncolysate trial. J Am Coll Surg. 1998;187(1):69-79.
  14. Kimura H, Yamaguchi Y. A phase III randomized study of interleukin-2 lymphokine-activated killer cell immunotherapy combined with chemotherapy or radiotherapy after curative or noncurative resection of primary lung carcinoma. Cancer. 1997;80(1):42-49.
  15. Ratto GB, Zino P, Mirabelli S, et al. A randomized trial of adoptive immunotherapy with tumor-infiltrating lymphocytes and interleukin-2 versus standard therapy in the postoperative treatment of resected nonsmall cell lung carcinoma. Cancer. 1996;78(2):244-251.
  16. Law TM, Motzer RJ, Mazumdar M, et al. Phase III randomized trial of interleukin-2 with or without lymphokine-activated killer cells in the treatment of patients with advanced renal cell carcinoma. Cancer. 1995;76(5):824-832.
  17. Kimura H, Yamaguchi Y. Adjuvant immunotherapy with interleukin 2 and lymphokine-activated killer cells after noncurative resection of primary lung cancer. Lung Cancer. 1995;13(1):31-44.
  18. Gold JE, Malamud SC, LaRosa F, et al. Adoptive chemoimmunotherapy for the treatment of relapsed and refractory solid tumors using ex vivo activated memory T cells (autolymphocyte therapy) and cyclophosphamide. J Immunother. 1993;13(3):213-221.
  19. Graham S, Babayan RK, Lamm DL, et al. The use of ex vivo-activated memory T cells (autolymphocyte therapy) in the treatment of metastatic renal cell carcinoma: Final results from a randomized, controlled, multisite study. Semin Urol. 1993;11(1):27-34.
  20. Lavin PT, Maar R, Franklin M, et al. Autolymphocyte therapy for metastatic renal cell carcinoma: Initial clinical results from 335 patients treated in a multisite clinical practice. Transplant Proc. 1992;24(6):3059-3064.
  21. Koretz MJ, Lawson DH, York RM, et al. Randomized study of interleukin 2 (IL-2) alone vs IL-2 plus lymphokine-activated killer cells for treatment of melanoma and renal cell cancer. Arch Surg. 1991;126(7):898-903.
  22. Figlin RA, Thompson JA, Bukowski RM, et al. Multicenter, randomized, phase III trial of CD+ tumor-infiltrating lymphocytes in combination with recombinant interleukin-2 in metastatic renal cell carcinoma. J Clin Oncol. 1999;17:2521-2529..
  23. Morse MA, Clay TM, Lyerly HK. Current status of adoptive immunotherapy of malignancies. Expert Opin Biol Ther. 2002;2(3):237-247.
  24. Mitchell DA, Fecci PE, Sampson JH. Adoptive immunotherapy for malignant glioma. Cancer J. 2003;9(3):157-166.
  25. Yamaguchi Y, Ohshita A, Kawabuchi Y, et al. Adoptive immunotherapy of cancer using activated autologous lymphocytes--current status and new strategies. Hum Cell. 2003;16(4):183-189.
  26. Koehl U, Sorensen J, Esser R, et al. IL-2 activated NK cell immunotherapy of three children after haploidentical stem cell transplantation. Blood Cells Mol Dis. 2004;33(3):261-266.
  27. Coppin C, Porzsolt F, Awa A, et al. Immunotherapy for advanced renal cell cancer. Cochrane Database Syst Rev. 2004;(3):CD001425.
  28. Oelke M, Krueger C, Schneck JP. Technological advances in adoptive immunotherapy. Drugs Today (Barc). 2005;41(1):13-21.
  29. Rossig C, Brenner MK. Genetic modification of T lymphocytes for adoptive immunotherapy. Mol Ther. 2004;10(1):5-18.
  30. Oelke M, Krueger C, Schneck JP. Technological advances in adoptive immunotherapy. Drugs Today (Barc). 2005;41(1):13-21.
  31. McGavern DB. Immunotherapeutic relief from persistent infections and amyloid disorders. Neurology. 2006;66(2 Suppl 1):S59-S64.
  32. Yamaguchi Y, Hihara J, Hironaka K, et al. Postoperative immunosuppression cascade and immunotherapy using lymphokine-activated killer cells for patients with esophageal cancer: Possible application for compensatory anti-inflammatory response syndrome. Oncol Rep. 2006;15(4):895-901.
  33. McKee MD, Fichera A, Nishimura MI. T cell immunotherapy. Front Biosci. 2007;12:919-932.
  34. Parmiani G, Castelli C, Santinami M, Rivoltini L. Melanoma immunology: Past, present and future. Curr Opin Oncol. 2007;19(2):121-127.
  35. Wysocki PJ, Zolnierek J, Szczylik C, Mackiewicz A. Recent developments in renal cell cancer immunotherapy. Expert Opin Biol Ther. 2007;7(5):727-737.
  36. Thistlethwaite FC, Elkord E, Griffiths RW, et al. Adoptive transfer of T(reg) depleted autologous T cells in advanced renal cell carcinoma. Cancer Immunol Immunother. 2008;57(5):623-634.
  37. Kondo H, Hazama S, Kawaoka T, et al. Adoptive immunotherapy for pancreatic cancer using MUC1 peptide-pulsed dendritic cells and activated T lymphocytes. Anticancer Res. 2008;28(1B):379-387.
  38. Kimura H, Iizasa T, Ishikawa A, et al. Prospective phase II study of post-surgical adjuvant chemo-immunotherapy using autologous dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes in primary lung cancer patients. Anticancer Res. 2008;28(2B):1229-1238.
  39. Bernhard H, Neudorfer J, Gebhard K, et al. Adoptive transfer of autologous, HER2-specific, cytotoxic T lymphocytes for the treatment of HER2-overexpressing breast cancer. Cancer Immunol Immunother. 2008;57(2):271-280.
  40. Motohashi S, Nakayama T. Clinical applications of natural killer T cell-based immunotherapy for cancer. Cancer Sci. 2008;99(4):638-645.
  41. Till BG, Jensen MC, Wang J, et al. Adoptive immunotherapy for indolent non-Hodgkin lymphoma and mantle cell lymphoma using genetically modified autologous CD20-specific T cells. Blood. 2008;112(6):2261-2271.
  42. Hersey P, Halliday GM, Farrelly ML, et al. Phase I/II study of treatment with matured dendritic cells with or without low dose IL-2 in patients with disseminated melanoma. Cancer Immunol Immunother. 2008;57(7):1039-1051.
  43. Cannon MJ, O'Brien TJ. Cellular immunotherapy for ovarian cancer. Expert Opin Biol Ther. 2009;9(6):677-688.
  44. Chekmasova AA, Brentjens RJ. Adoptive T cell immunotherapy strategies for the treatment of patients with ovarian cancer. Discov Med. 2010;9(44):62-70.
  45. Rolle CE, Sengupta S, Lesniak MS. et al. Challenges in clinical design of immunotherapy trials for malignant glioma. Neurosurg Clin N Am. 2010;21(1):201-214.
  46. Di Stasi A, Tey SK, Dotti G, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673-1683.
  47. Sakamoto M, Nakajima J, Murakawa T, et al. Adoptive immunotherapy for advanced non-small cell lung cancer using zoledronate-expanded γδTcells: A phase I clinical study. J Immunother. 2011;34(2):202-211.
  48. Yamasaki K, Horiguchi S, Kurosaki M, et al. Induction of NKT cell-specific immune responses in cancer tissues after NKT cell-targeted adoptive immunotherapy. Clin Immunol. 2011;138(3):255-265.
  49. Kurosaki M, Horiguchi S, Yamasaki K, et al. Migration and immunological reaction after the administration of αGalCer-pulsed antigen-presenting cells into the submucosa of patients with head and neck cancer. Cancer Immunol Immunother. 2011;60(2):207-215.
  50. Doskali M, Tanaka Y, Ohira M, et al. Possibility of adoptive immunotherapy with peripheral blood-derived CD3⁻CD56+ and CD3+CD56+ cells for inducing antihepatocellular carcinoma and antihepatitis C virus activity. J Immunother. 2011;34(2):129-138.
  51. Rapoport AP, Aqui NA, Stadtmauer EA, et al. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood. 2011;117(3):788-797.
  52. Geller MA, Cooley S, Judson PL, et al. A phase II study of allogeneic natural killer cell therapy to treat patients with recurrent ovarian and breast cancer. Cytotherapy. 2011;13(1):98-107.
  53. Weber J, Atkins M, Hwu P, et al; Immunotherapy Task Force of the NCI Investigational Drug Steering Committee. White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: A report of the CTEP subcommittee on adoptive cell therapy. Clin Cancer Res. 2011;17(7):1664-1673.
  54. Zhong JH, Li H, Li LQ, et al. Adjuvant therapy options following curative treatment of hepatocellular carcinoma: A systematic review of randomized trials. Eur J Surg Oncol. 2012;38(4):286-295.
  55. Tang X, Liu T, Zang X, et al. Adoptive cellular immunotherapy in metastatic renal cell carcinoma: A systematic review and meta-analysis. PLoS One. 2013;8(5):e62847

Cellular Therapy:

  1. Barrett S. Cellular therapy. 2003. Available at: www.quackwatch.org/01QuackeryRelatedTopics/Cancer/cellular.html. Accessed June 26, 2013.
  2. American Cancer Society. Cell therapy. Last Revised: November 1, 2008. Available at: http://www.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/cell-therapy. Accessed on June 26, 2013.
  3. Centers for Medicare and Medicaid Services. National Coverage Determination for Cellular Therapy. NCD #30.8. Available at: http://www.cms.gov/medicare-coverage-database/details/ncd-details.aspx?NCDId=6&ncdver=1&CoverageSelection=Both&ArticleType=All&PolicyType=Final&s=All&KeyWord=cellular+therapy
    &KeyWordLookUp=Title&KeyWordSearchType=And&bc=gAAAACAAAAAA&
    . Accessed on June 26, 2013.


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