Tumor Immunology and Immunotherapy

av Kristina Witt, 20 - 23 oktober 2016

AACR – Tumor Immunology and Immunotherapy in Boston, USA

The AACR special conference ‘Tumor Immunology and Immunotherapy’ is the 6th in its series. More than 800 participants from academia and life science industry discussed new strategies on harnessing the immune system for treatment and prevention of different cancers. The conference was held in Boston, a scientific hub with academic research, life science startups and established pharmaceutical companies in local proximity.

The conference covered 8 sub-disciplines from the tumor microenvironment and immune modulation to biomolecular engineering of immune responses, imaging and single-cell analysis. This wide range of topics reflects the diversity of the tumor immunology field and the great variety of strategies investigated to induce/enhance anti-tumor immunity in patients.

Tyler Jacks, MIT, discussed in his key note lecture the importance of genetic engineered mouse models for cancer research. Choosing the correct model is of great importance. Several studies have shown that immune regulation of tumors in vivo is dependent on the context and localization. Syngeneic mouse models are preferable to study tumor development and the influence of immune suppression. On the other hand are PDX models, lacking most of the immune subsets, used to study direct anti-tumor effector functions against human tumors. Secondly, tumor localization is of great importance in in-vivo studies. The local environment can shape the tumor microenvironment from immune stimulating to immune suppressive.

Antoni Ribas from UCLA Medical Center, Los Angeles present his work on why melanoma patients relapse after anti-PD-1 treatment. For his study he compared tumor samples the sites before checkpoint blockade treatment and the compared it with tumor tissue at the same site after relapse. Ribas identified in 2 patients mutations in the JAK1 and 2 upon anti-PD-1 treatment resulting in downregulation of PD-L1, one target of this pathway, on the tumor cells. With the lack of PD-L1, T cells expressed lower levels of PD-1 and became insensitive to anti-PD1 treatment. Studies in 2 other patients identified different mutations. Overall are the resistance mechanisms in patients to checkpoint blockade heterogeneous and can’t be generalized. Even different relapse sites have been shown to undergo different mechanisms of evasion.

One focus of the conference was improvement and novel strategies for CARs (Chimeric Antigen Receptors). Michael Sadelain, Memorial Sloan Kettering, New York, discussed challenges in the field of CAR therapy as vector and transduction strategies. He presented data on a CRISPR based targeted integration of CAR vectors. This targeting integration improved the expression of the CAR as well as the survival and function of the T cells.  Yvonne Chen from UCLA presented a bi-specific CAR targeting both CD19 and CD20. The signaling only requires engagement with one target antigen and can control lymphomas (CD19+ and CD20+) evading CD19 CARs by downregulation of CD19. Wendell Lim from the University of California presented his work on CAR engineering for improved target specificity. His group developed a genetic system that is based on the recognition of 2 antigens. A Receptor recognizing antigen A induces intracellular the expression of the CAR recognizing antigen B. This system is a conditional CAR. Only if antigen A is encountered will the CAR be expressed. This enables a site specific CAR expression and potentially reduces off-site CAR mediated cytotoxicity.

Overall a wide range of new strategies on improving existing immune-based anti-tumor therapies were discussed at the meeting. Further is it of great importance to better understand the intra- and inter-tumoral heterogeneity to improve precision medicine and tackle the existing challenges.

Attending the conference enabled me to learn about novel ideas and methods in the field of tumor immunology and immunotherapy that we can incorporate in our work. It was an inspiring meeting with many interesting scientific discussions. I would like to thank Radiumhemmets Forskningsfonder for the opportunity to participate in the AACR Conference.