Cancer vaccines have the goal to apply what has been done for a few infectious diseases and focus the power of human immunity on eliminating tumor cells. There are encouraging signs that this aim is achievable, but success remains elusive: a review recently published on Cell now focuses on the multiple unique challenges faced by vaccines targeting cancer, trying to point out a future strategy to overcome the difficulties in the field.
Tumors are not acute foreign events, but rather evolve from and within the host and are only apparent clinically after the escape from the immune pressure that controls incipient neoplasms; moreover, surviving tumor cells accumulate intrinsic defenses to support their escape, resulting in a complex and immunosoppressant microenvironment. In addition, cancer possess enormous molecular diversity and is not a disease, but a thousand of diseases, making target identification a difficult task. Thus, therapeutic cancer vaccines face distinct challenges from prophylactic vaccines for infectious pathogens. However, authors say that «Numerous technological advances – from mass spectrometry and machine learning in neoantigen prediction, to genetically and pharmacologically engineered mouse models, to advances in single-cell transcriptomics and genomics – have revealed new biology and point to how to bridge this divide». The review focuses mostly on those aspects that are translationally relevant, such as antigen selection and delivery, as well as unique challenges, like the immunosuppressive tumor-immune microenvironment and how to gather evidence for vaccine efficacy. Authors point out that promising approaches share the theme of dying whole-tumor cells (WTC): «Simpler than using the latest sequencing and bioinformatic tools to find the ‘‘best’’ antigens, and less biased from incomplete knowledge, WTC vaccines rely on the undefined antigens within a tumor», authors say. «By mimicking the stressed and dying cells that are the starting point of natural immunity, they provide access to all the antigens of the cell, at levels reflective of what is in the cell, and without any observer selection or bias, potentially providing a clearer image of a personal tumor than any technology can yet deliver. The importance of tumor-specific T cells to immune therapy and to durable patient survival cannot be overemphasized: cancer vaccines have been proven to enhance both the number of such cells and their repertoire, but there are still difficult waters to cross to arrive at the induction of truly effective T cell populations to achieve a lifeline to cure for our patients», authors conclude.