SDSC meeting sponsored by Life Tech 1/30/14
Dr Alan Epstein Keck School of Medicine Cancer Immunotherapy
On the first SDSC meeting of 2014, Life Tech sponsored the meeting at Green Acre at the Nautilus location. Future meetings will take place at the Green Acre at the Eli Lilly site. Carina Torres and Cheryl Kim gave announcements at the beginning of the meeting. The So Cal Flow Summit meeting will take place in Irvine, Mar. 24- 25, http://socalflow.org. This will be a 2 day meeting to visit with other flow cytometry users and hear talks about recent research using flow cytometry. There will be a basic flow training before the meeting and training on necrobiology after.
Dr Epstein began his talk describing the hallmarks of cancer, including the way it avoids the immune system by using mechanisms that the fetus uses to protect itself from the maternal environment. There are different methods of cancer immunotherapy including: vaccines and adjuvants, adoptive immunotherapy, cytotoxic antibodies, blockade of growth factors, and reversal of immune tolerance and suppression. Many of these therapies do not work alone, but in conjunction with others. A vaccine alone typically doesn’t work without converting the tumor microenvironment into an inflammatory environment, allowing the body’s natural immune response to aid the vaccine.
Obstacles to cancer immunotherapy include cellular suppression and molecular suppression. Cellular suppressors, such as T regs, myeloid derived suppressor cells (MDSC), and type 2 tumor associated macrophages (TAM), are used by the tumor to avoid detection by the immune system. Likewise, molecular suppressors, such as loss of HLA I and increase of HLA G, resistance to CTLs using B7-H4, PD 1&2, and CTLA4, and release of factors TGFb, IDO, and IL-10 are ways that cancer cells avoid detection and elimination. To get a successful immunotherapy response, the suppressors need to be removed.
Dr Epstein’s lab has been approaching immunotherapy using syngeneic mouse models. Treatment requires a strong immunostimulation and a reversal of immunosuppression. Their research includes targeted delivery of a TLR agonist to the tumor using an antibody:CpG conjugate. They have an antibody against the TNT3 which targets necrotic centers of tumors. Conjugated to CpG, it is taken up only in tumors, as seen in radiological studies done in China. Using MDSC markers, CD11b and CD33, they have successfully detected early tumors in patients, including 2 “healthy donors” that were diagnosed with cancer 3 months after the study. They hope to use these markers as an early diagnosis to guide doctors in their therapeutic regimens. The last part of their research is studying hematopoetic reconstitution following lymphopenia. They showed that IL12 treatment after chemotherapy increased granulocyte recovery much faster than without treatment. They used a no lyse/no wash protocol to allow for a more rapid assay.
This was a very informative meeting with a large turnout. I look forward to the next one.