Anti-idiotype cancer vaccine 105AD7(The University of Nottingham Students' Union)

Purpose: To assess the tolerability and effectiveness of 105AD7 vaccination in colorectal cancer patients. 105AD7 is a human anti-idiotypic antibody mimicking CD55, a glycoprotein, which is more than expressed on colorectal cancer cells and protects them from attack by complement.Experimental Design: Colorectal cancer patients (n = 67) eligible for primary surgery were randomized to receive the anti-idiotypic antibody 105AD7±Bacillus Calmette-Guerin/alum or to no treatment (control group). The immunizations were given i.d./i.m. before surgery and continued for a period of 2 years. The patients were monitored in enzyme-linked immunospot (ELISPOT; γ-IFN), proliferation assay, and Luminex cytokine assays.Results: No serious adverse events were recorded. Of the 32 investigated immunized patients, 14 (44%) were considered to be responders in the ELISPOT assay. Induced proliferative responses were noted in 17 of 40 (43%) monitored patients. There was no correlation between the ELISPOT and proliferation assays. Luminex analyses revealed tumor necrosis factor-α and granulocyte macrophage colony-stimulating factor responses not only to the vaccine but also toward the native antigen CD55 in 9 of 13 (69%) patients.Conclusions: Immune responses to vaccination were induced in a majority of monitored patients measured by ELISPOT and proliferation assay. The lack of correlation between the ELISPOT and proliferation assays may reflect the fact that the two methods measure different T-cell responses and highlights the importance of multiple readouts in evaluating a potential cancer vaccine. Responses to both the anti-idiotype and the CD55 antigen were measurable, adding support to the use of CD55 as a target in cancer treatment.

105AD7 is a human monoclonal antibody that mimics the complement regulatory protein, CD55, overexpressed by many solid tumours including osteosarcoma. This study was designed to assess the toxicity and efficacy of this vaccine in a young age group of patients within 1-6 months of myleosuppressive chemotherapy. Out of 28, 20 (71%, 95% CI 51-87%) patients showed a significant T-cell proliferation response in vitro to the 105AD7 protein but not to human IgG. Furthermore, 13 out of 22 (59%, 95% CI 36-79%) patients showed antigen-specific gammaIFN secretion (range 20-370 U/ml). Nine out of 28 (32%, 95% CI 16-52%) patients made weak antibody responses to CD55. This study showed that 105AD7 was well tolerated in younger patients with osteosarcoma. In addition, two patients with possible clinical responses were given compassionate permission to continue immunisation quarterly for 2 years. They both remain alive and disease free 5.8 and 6.5 years from original diagnosis of osteosarcoma and showed no adverse effects of repeated immunisation. In conclusion, the majority of patients showed measurable T helper responses when vaccination was commenced within a 6-month window of intensive chemotherapy with no clinically significant toxicity. Future clinical trials incorporating immune stimulation strategies should include early introduction of vaccines during the highest risk period for relapse.