Cancer patient vaccination

Parmiani N, et al. T-cell response to unique and shared antigens and vaccination of cancer patients. Cancer Immunol 2002 2 6. 

Table 2. Composition of commercial vaccines used as therapeutic vaccines in cancer patients.

Vaccines generally used sialylated (s)Tn, which are mucin epitopes expressed on epithelial tumors, conjugated with KLH. This vaccine was commercialized as Theratope (Biomira Inc., Edmonton, Canada). In a phase I study O Boyle et al. [199] injected the vaccine to colorectal cancer patients. Toxicity was only local, and an antibody response was observed. 

Several trials were performed on breast cancer patients treated with cyclophosphamide. Little local toxicity was found, and an antibody response was evidenced. Partial clinical responses and disease stabilizations were obtained. [200-202]. Adluri et al. [203] compared vaccines using Detox or QS-21 in an adjuvant therapy for colorectal cancer patients. Toxicity was mostly local. An antibody response was... 

In another study involving patients with metastatic breast, colorectal and ovarian cancer, increased anti-sTn titers were correlated with better survival. Even if before treatment, elevated titers of antibodies against the mucin MUC1, were correlated with a poor response to immunotherapy, CTL precursors to the MUC1 were detected in carcinoma patients [208], A vaccine using 10 pg/ml MUC1-KLH mixed with Detox was injected s.c. in breast cancer patients treated with cyclophosphamide. A weak antibody response, and an ex vivo CTL response against HLA-matched adenocarcinoma cell lines were seen. No correlation with the clinical outcome was available [209],... 

Since point mutations of the ras proto-oncogene are often found in cancer, a vaccine was made with mutated ras peptides mixed with Detox. In a phase I study, CD4+ proliferation and CD8+ cytotoxicity specific to the mutated peptide, were observed. The side effects were minimal and one patient showed a stabilisation of the disease [213],... 

Table 3. List of clinical trials performed with lipids A as adjuvant of therapeutic vaccines administered to cancer patients.

Because it requires small amounts of lipid A generally injected s.c., the adjuvant effect of lipid A has been largely investigated in cancer patients, but only with MPLA. Phase I and phase II trials show weak toxicity of different vaccines with MPLA and the development of an immune response. Phase III are now necessary to find an effective protocol. 

The overexpression of HER-2 protein in cancer cells makes it an ideal target for vaccines and other targeting strategies. Vaccines optimized to induce maximum T cell immunity to HER-2 may lead to potent in vivo antitumor immunity. HER-2 protein has been evaluated as a potential target for the development of cancer vaccines because preexistent T cell and antibody responses to HER-2 have been described in breast cancer patients (Disis and Cheever, 1996). In other words, breast cancer patients have preexisting immunity to the HER-2 receptor in the form of elevated antibody titers and T cell immunity. Elevated anti-HER-2 T cell responses have been demonstrated in breast and ovarian cancer patients following immunization with peptides derived from the HER-2 protein (Disis et al., 1999). However, whether peptide-specific T cell responses can be translated to antitumor immunity has yet to be established. 

Jiang, X. P., Yang, D. C., Elliot, R. L., and Head, J. F. 1999. Reduction in serum IL-6 after vaccination of breast cancer patients with tumor-associated antigens is related to estrogen receptor status. Cytokine 72 458 165. 

Atanackovic, D., Altorki, N.K., Cao, Y., Ritter, E., Ferrara, C.A., Ritter, G., Hoffman, E.W., Bokemeyer, C., Old, L.J., Gnjatic, S. Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming. Proc Nat Acad Sci USA 105 (2008) 1650-1655. 

The acceptable level of toxicity for an adjuvant will depend on its application. For adjuvants intended for use in therapeutic vaccines the level will be higher than for those intended for prophylactic vaccines in healthy individuals. This is particularly true of therapeutic vaccines intended for treatment of cancer patients or life-threatening infectious disease. 

Liebtich, W., Schlag, R, Manasterski, M., Lehner, B., Stohr, M., Moller, R. and Schirrmacher, V. (1991). In vitro and clinical characterisation of a Newcastle disease virus-modified autologous tumor cell vaccine for treatment of colorectal cancer patients. Eur. J. Cancer 27, 703-710. 

Clinical Outcome of Breast and Ovarian Cancer Patients Treated after High-Dose Chemotherapy and Autologous Stem Cell Rescue with Theratope (STn-KLH) Cancer Vaccine Theratope (STn-KLH) Cancer Vaccine following Autologous Transplant... 

The associations of immune function parameters with EPS and OS in vaccinated breast cancer patients were estimated via Cox regression models. The immune response results were split in groups by the median values, with the medians determined separately for each vaccine group, and the resulting categories combined. The potential for differential effects of immune response and vaccine formulation across relapse risk groups was tested using interaction terms. 

Among breast cancer patients alone, the IgG antibody titer to STn was statistically signiftcantly higher after vaccination with the second formulation compared to the first formulation (p=.009). The IgG antibody titer to OSM was marginally statistically significant higher after vaccination with the second formulation compared to the first formulation (p=.08) and were thus used to evaluate outcome. 

Factors associated with EFS in Vaccinated Breast Cancer Patients... 

Since breast cancer patients were the largest group of patients treated with the two different formulations of Theratope vaccine, we. focused again on evaluating the outcome after vaccination as a function of in vitro immunological responses. Fifty-three patients were available for this analysis. 

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