Immunotherapy of cancer: key findings and commentary on the third Tegernsee conference

Abstract

Cancer immunotherapy broadly includes active immunization, as in the use of cancer vaccines, passive immunization, such as the use of adoptive cell therapy and antibodies that modulate tumor function, and immunostimulation, using antibodies and small molecules to treat malignancy by activating or unleashing an endogenous immune response against tumor cells. Currently, >100 different monoclonal antibodies are in use or under evaluation for use as therapeutic agents in various malignancies. Active stimulation of the host's immune system holds promise for achieving durable remission of malignant disease and represents a nontoxic method of therapy if tumor-specific effector cells can be selectively targeted. However, no active-specific treatment strategy (i.e., a therapeutic cancer vaccine) has yet found its way into the clinical armamentarium, although several promising recent reports suggest that, for follicular lymphoma, prostate cancer, and melanoma, clinical benefit was shown for the first time in randomized trials with a vaccine approach. Here, we report on the key findings of the Third Tegernsee Conference on Immunotherapy of Cancer (Feldafing, Germany, July 2-4, 2009) and provide short commentaries on data presented at this meeting regarding the future role of cancer vaccines, recent developments in adoptive cellular therapy, ways to improve immunotherapeutic treatment modalities (e.g., by manipulating the tumor microenvironment), and some novel targeted therapies that are well advanced in clinical testing, all of which have implications for future oncology practice.

Figure 1.

Proposed mechanism of action for cancer vaccines. Tumor antigens (e.g., administered as proteins, peptides, or whole tumor cells) are taken up and processed by specialized antigen-presenting cells (APCs) such as dendritic cells (DCs). DCs migrate to the vaccine-draining lymph nodes and present relevant antigens to CD8⁺ T lymphocytes, which, in turn, are able to recognize tumor cells throughout the body and destroy them by several effector mechanisms such as the perforin/granzyme pathway, direct cell–cell interaction (e.g., Fas/Fas ligand), or certain mediators (e.g., INFγ). Not shown but also of importance are B lymphocytes, CD4⁺ T helper cells and cells of the innate immune system such as natural killer cells and macrophages. Abbreviations: INF, interferon; MHC, major histocompatibility complex.