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.

Simultaneous TLR2 inhibition and TLR9 activation synergistically suppress tumor metastasis in mice

“…Treg numbers in the circulation of TLR2-deficient mice are reduced compared with their WT littermate controls [10] . Furthermore, the activation of the TLR2 signal may be crucial for tumor cells to escape killing by the host [29] . Huang et al recently found that activation of TLR2 on cancer cells by Listeria monocytogenes promotes tumor growth [30] , while Kim et al reported that activation of TLR2 by an extracellular matrix proteoglycan versican of Lewis lung carcinoma stimulates pro-tumor inflammation and metastasis [13] .…”

“…Increasing evidence has shown that not only are there insufficient numbers of antitumor effector cells but that there are also too many immunosuppressive factors in tumor environment, which culminates in the failure to eradicate tumor cells [2,3] . Thus, a rational anti-cancer immunotherapeutic strategy should include both anti-tumor immune elements and elements able to eliminate tumor-induced immunosuppressive factors [4] .…”

A tritherapy combination of a fusion protein vaccine with immune‐modulating doses of sequential chemotherapies in an optimized regimen completely eradicates large tumors in mice

“…[1][2][3] The tumor microenvironment represents a consistently effective barrier to clinical responses. 4 The need to design novel strategies based on targeting not only the tumor but also its microenvironment arises urgently.…”

New Insights into the Role of the Immune Microenvironment in Breast Carcinoma

“…Available data support the hypothesis of an immune-mediated antitumor activity in breast carcinoma, and several lines of research are ongoing [90]. It is critical to understand what happens in the tumoral microenvironment in order to design biological agents that may modulate the immune response towards cancer cell destruction (Figure 2).…”