Science Due Diligence

There have been many past failures of cancer vaccine treatments made up of agnostic cellular or protein vaccines. This was probably due to the lack of understanding of the degree of genomic heterogeneity of the individual tumors and the lack of understanding of host tumor interactions. This has drawn attention to the use of personal cancer vaccines either alone or in combinatorial treatment modalities. A technical review of this is provided.

Unlocking the Potential of Cancer Vaccines: The Clinical Ramifications of Antigen Competition Driven Immunoediting:

We have presented the conceptual and practical justification for Active (Patient specific) Immunotherapy (ASI) vaccination in preventing progression of post resection, minimal residual disease, both in a unique syngeneic guinea pig model and in a successful Phase III clinical trials in colon cancer. The basis of this personal treatment success is the interaction of two known immune functions, antigen competition and immune editing. The result of these host tumor interactions is a sculpting of the tumor from a diverse array of immunogenic tumor cell clones, ranging from weak to strong antigens, to a restricted set of weakly immunogenic clones.

These clones can survive and kill an immunocompetent host due to immune tolerance. The personal immunization is administered intradermally with a critical number of live, irradiated (nontumorigenic) cells. The autologous tumor cells are admixed with TICE BCG, an adjuvant capable of eliciting a strong innate immune response and recruiting and trafficking large numbers of immunocompetent progenitor cells to the vaccination sites. This reaction cannot be achieved with tumor cells alone and the resultant tumor specific immunity cannot be achieved with BCG alone.

This compounded vaccination breaks immune tolerance and provides a robust immune reaction that consists of cytotoxic T cells and strong immunologic memory. The clinical benefit, particularly in the unmet medical need of stage II (T3 &T4 a & b) colon cancer is a highly significant recurrence free-survival benefit, with an actual durability of 15 years. Also, the tumor specific immune response in these patients provided biological resources (tumor specific Human Monoclonal Antibodies) the targets of which, have been partially characterized and immunologically tested for identifying mutant neoantigens and thus neoepitopes. These will foster research and development of natural therapeutic and prophylactic adenocarcinoma vaccines.

These important correlates of the host tumor interactions that lead to the prevention of progress of minimal residual disease support the potential of combinatorial treatments of personal ASI to achieve important clinical benefits of standard treatments of advanced disease patients is the authentic and exact new beginning of immunotherapy.