61IN - Rational Combinations in Cancer Immunotherapy

Abstract

ABSTRACT Immunotherapy of cancer encompasses different strategies that elicit or enhance the immune response against tumors. These include procedures to make tumors look more immunogenic, formulated cancer vaccines, adoptive transfer of immune cells and the use of immunomodulating factors. As successfully thought in many other examples of advances in the history of medicine, combinations are likely to be the key to achieve meaningful and unprecedented survival benefit for cancer patients. Examples of successful combinations can be found in the development of chemotherapies for infectious disease, leukemia or cancer of the testicle. Making the most of cancer immunotherapy would require the identification of synergistic combinations of the various immunotherapy approaches or of different elements within each of the immunotherapy approaches. Ample evidence also indicates that conventional therapies of cancer can also be efficaciously combined with immunotherapy. Immunotherapy strategies combined among themselves frequently offer evidence for synergistic effects. The rationale typically involves different but complementary mechanisms of action, eventually impinging on more than one immune system mechanism. In this regard, enhancing numbers of tumor-antigen primed T lymphocytes and simultaneously or sequentially using immunomodulation compounds to remove inhibitory checkpoints or/and agonistically act on immunostimulatory receptors enjoys both a strong rationale and solid preclinical evidence. As a prominent example of efficacious combinations, the simultaneous blockade of PD-1 and CTLA-4 is giving rise to therapeutic synergy, while still offering room for efficacy improvement. Nonetheless, combinations of immunotherapies with immunotherapies are not the only viable options. Animal models suggest that immunotherapies in combination with chemotherapy, radiotherapy, targeted molecules and debulking surgery are likely to radically change cancer treatment paradigms. Advancing the field of combinatorial immunotherapy will require changes in the way several investigational agents are combined early on in development and will require novel experimental end-points that would permit faster and safer progress. Disclosure: I. Melero: Advisory board to Bristol-Myers squibb, Roche-Genentech, Takeda, Miltenyi Biotec.