Dendritic cells (DCs) are the most potent type of antigen presenting cells and are vital in inducing activation and proliferation of T-lymphocytes. Their unique property has prompted their recent application to therapeutic cancer vaccines. Isolated DCs containing tumor antigen ex-vivo and administered as a cellular vaccine, have been found to induce protective and therapeutic anti-tumor immunity in experimental animals.
The clinical evaluation of DC immunotherapy in humans is in its earliest phases for the treatment of malignancies such as leukemia, lymphoma, melanoma, and certain solid tumors. Specifically, melanoma-associated antigens have been characterized at the molecular level and melanoma vaccine is currently being investigated in clinical trials. Dendritic cells immunotherapy involves isolating dendritic cells from either circulating blood or bone marrow cells from the patient (or HLA-matched donor) and then exposing them to proteins from the patient's cancer cells in order to activate T-lymphocytes. These lymphocytes are grown in bioreactors to be infused into the patient when sufficient numbers have been obtained.
Currently, no conclusions regarding the efficacy of DC immunotherapy can be made from the anecdotal reports reported in the published, peer-reviewed medical literature. Although DC immunotherapy appears to be a promising modality for the treatment of cancer, completion of randomized trials is necessary. Specifically, the appropriate antigen(s), adjuvant(s), dose, route and schedule need to be established. In a review of the evidence, Figdor et al (2004) concluded that “[a]lthough early clinical trials indicate that [dendritic cell] vaccines can induce immune responses in some cancer patients, careful study design and use of standardized clinical and immunological criteria are needed”.
Ardon et al (2012) noted that DC-based tumor vaccination has rendered promising results in relapsed high-grade glioma patients. In the HGG-2006 trial (EudraCT 2006-002881-20), feasibility, toxicity, and clinical efficacy of the full integration of DC-based tumor vaccination into standard post-operative radiochemotherapy were studied in 77 patients with newly diagnosed glioblastoma. Autologous DC was generated after leukapheresis, which was performed before the start of radiochemotherapy. Four weekly induction vaccines were administered after the 6-week course of concomitant radiochemotherapy. During maintenance chemotherapy, 4 boost vaccines are given. Feasibility and progression-free survival (PFS) at 6 months (6mo-PFS) were the primary end points. Overall survival (OS) and immune profiling, rather than monitoring, as assessed in patients' blood samples, were the secondary end points. Analysis has been done on intent-to-treat basis. The treatment was feasible without major toxicity. The 6mo-PFS was 70.1 % from inclusion. Median OS was 18.3 months. Outcome improved significantly with lower EORTC RPA classification. Median OS was 39.7, 18.3, and 10.7 months for RPA classes III, IV, and V, respectively. Patients with a methylated MGMT promoter had significantly better PFS (p = 0.0027) and OS (p = 0.0082) as compared to patients with an un-methylated status. Exploratory "immunological profiles" were built to compare to clinical outcome, but no statistical significant evidence was found for these profiles to predict clinical outcome. The authors concluded that full integration of autologous DC-based tumor vaccination into standard post-operative radiochemotherapy for newly diagnosed glioblastoma seems safe and possibly beneficial. They stated that these results were used to power the currently running phase IIb randomized clinical trial.
In a systematic review, Tanyi et al (2012) stated that after decades of extensive research, epithelial ovarian cancer still remains a lethal disease. Multiple new studies have reported that the immune system plays a critical role in the growth and spread of ovarian carcinoma. These investigators summarized the development of DC vaccinations specific for ovarian cancer. So far, DC-based vaccines have induced effective anti-tumor responses in animal models, but only limited results from human clinical trials are available. Although DC-based immunotherapy has proven to be clinically safe and efficient at inducing tumor-specific immune responses, its’ clear role in the therapy of ovarian cancer still needs to be clarified. The relatively disappointing low-response rates in early clinical trials point to the need for the development of more effective and personalized DC-based anti-cancer vaccines.
CPT Codes / HCPCS Codes / ICD-9 Codes
There is no specific CPT code for dendritic cell immunotherapy:
ICD-9 codes not covered for indications listed n the CPB:
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