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4 months in the placebo group. (P=0.01) [Kyogo et.al] an earlier study by Nestle et.al (1998) had showed promising results. In that study, a small group of renal cancer patients were vaccinated with RNA-transfected dendritic cells. T cell response was noted in most of the treated patients and a follow up study conducted after 19 months showed that 7 out of 10 patients still survived. [Jian et.al, 2008] Other vaccines such as the 'Heat shock protein' (HSP) vaccine introduced in clinical trials have only showed mixed results and have not been responsive in all patients. Oncophage is one HSP that has been approved in Russia for renal cancer patients. [Kyogo et.al]
TREGS (a new outlook at Immunotherapy)
A relatively new and much less explored path in the immunotherapeutic research is the focus on the role of TREGS (regulatory T cells). All the techniques discussed above were concerned with boosting the host with additional T cells or tumor infiltrating Lymphocytes. However the results from these therapies have thus far only indicated marginal response. Hence, priming up the immune system may not be only solution to the problem. Also since tumors are intrinsic, any immunotherapy designed against it has the potential to cause autoimmune complications. Research has also shown that tumors evade the natural immunity by producing immunosuppressive factors such as IL-10 TGF-?, and VEGF. Therefore, immunotherapeutic research would be more effective if it also focuses on this immunosuppressive aspect of tumor. [Tyler J. Curial]
Tregs are involved in the immune evasive functions of tumor cells. Studying Tregs in the cancer microenvironment, therefore presents another approach to the treatment of cancer. It is known from previous studies that Tregs resemble CD4+CD25+ Leukemia cells. Using this phenotypical similarity, Barnett et.al (2005) studied the effects of the denileukin diftitox, an FDA approved antineoplastic agent, used in the treatment of T cell Lymphoma. Patients who underwent a single infusion of denileukin diftitox (9 or 12 ?g/kg) exhibited a remarkable reduction in Tregs. The results were similar for patients with different types of cancers for a period of 30 days. Another study by Dannull J., et al. (2005) also attested to reduced levels of Tregs and consequent reduction in suppression induced by CD4+CD25+ T cell in response to treatment with denileukin diftitox in renal cancer patients. Separate studies in mice have also indicated that Tregs suppression leads to more effective adoptive T cell therapy.
We are at the threshold of new and entirely different approach to the management of cancer. Though we are still in pursuit of effective cancer vaccines, Cancer Immunotherapy has developed much over the last decade. Many multi-antigenic cancer vaccines are now in the last phase of clinical trials. Personalized cancer treatment in the form of adoptive T cell therapies and entirely different perspectives of cancer research such as the Tregs suppression have provided more strength to our fight against cancer. In particular, this new outlook (Tregs suppression) complements the effect of the different types of cell transfer therapies that are aimed at increasing the immunity to cancer. Though we are still a long way from understanding all the intricate cellular mechanisms that underlie cancer, we are definitely witnessing a paradigm shift in immunotherapeutic treatment modalities and are fast progressing on our way to find a cure to this dreaded disease.
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6) Oikawa Takehir & Kawai Koji et.al, 'Adoptive transfer of autologous cytotoxic T. lymphocytes for metastatic renal cell carcinoma', Univ. Of Tsukuba, BCG, Vol 26, pg 39-41.
7) Tyler J. Curial, 'TREGS and Rethinking Cancer Immunotherapy', Journal of Clinical Investigation, Vol 117(5) May 2007, Available Online at, http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1857250
8) Dannull J., et al. Enhancement of vaccine-mediated antitumor immunity in cancer patients after depletion of regulatory T cells. J. Clin. Invest. 2005;115:3623 -- 3633.
9) Barnett B., Kryczek I., Cheng P., Zou W., Curiel T.J. Regulatory T cells…[continue]
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