Cancer vaccines come of age
Cancer vaccines represent a highly selective immune attack to tumors. However, previous cancer vaccines based on ‘classical’ tumor antigens (all self-antigens) failed to show significant clinical benefit. The recent success of Checkpoint Inhibitors (CI) and Adoptive Cell Therapy (ACT) and the innovation of Next Generation Sequencing (NGS) allowing fast and cheap tumor genome sequencing, have revealed: 1) the presence of bystander tumor-specific mutations with against which there is no immune tolerance, 2) the role of T cell immunity against these patient- and tumor-specific mutations in establishing clinical efficacy, and 3) the complex interplay between cells of the innate and adaptive immune system that reshape the tumor microenvironment. Most importantly, CI and ACT, are not limited to a specific tumor type, but have shown clinical activity in different tumor types. While representing a real ‘game changer’ in the field of cancer immunotherapy, both CI and ACT are endowed by significant side effects and present with additional limitations such as the low frequency of response for CI (about 20% long term survival) and the complex manufacturing process for ACT.
There is a need to develop alternative targeted T-cell based immunotherapeutic strategies to be used alone or in combination with CI to increase clinical efficacy.
During the last several years “targeted” immunotherapeutic approaches have come to prominence, the most successful of them being the development of therapeutic antibodies. Other targeted immuno-therapies based on cytolytic activity hold the promise of effective cancer treatments. For example, i) Antibody-Drug Conjugates, ii) antibodies driving T cells at the tumor site like T cell engaging bispecific antibodies, and iii) Chimeric Antigen Receptors (CARs) have achieved complete remissions in the treatment of advanced hematological malignancies. After a long “lag” phase also oncolytic viruses have been recently “validated” in advanced clinical studies.
Our strategy stems from recent therapeutic achievements in the fields of CI, therapeutic antibodies, cancer vaccines and oncolytic viruses. We plan to develop a series of new, potent immunotherapeutics capable of selectively killing tumor cells. Our immunotherapeutics embody the best features of oncolytic viruses and therapeutic antibodies, and include viral vectored genetic vaccines based on patient- and tumor-specific antigens.