04 Immunology

PROJECT SUMMARY/ABSTRACT
The Immunology Program includes 30 members (26 primary, 3 associate, 1 adjunct) from 9 departments. The
program is led by Dr. James Allison, an international authority on exploring fundamental mechanisms of the
immune response and checkpoint control, with co-leaders Dr. Jeffrey Molldrem, providing expertise in stem cell
and translational research, and Dr. Patrick Hwu, lending his extensive experience in novel vaccines and
adoptive T-cell therapies. The scientific goal of the Immunology Program is to conduct important studies in basic
immunology and translate the findings into effective cancer immunotherapy. The program focuses on 4 themes:
1) immune regulation, 2) immune checkpoint blockade, 3) cancer vaccines, and 4) T-cell therapies, each with a
specific aim: Aim 1: To understand fundamental mechanisms involved in regulating innate and adaptive immune
responses. Aim 2: To elucidate fundamental cellular and molecular mechanisms of immune checkpoints and
their impact on the tumor microenvironment by using preclinical models and clinical trials to identify the basis for
failure of response to therapy or relapse. Aim 3: To identify novel targets for cancer vaccine development that
will enable vaccination strategies to be more widely applied to the prevention and treatment of cancer. Aim 4:
To improve the success rate of T-cell-based therapies using a combinatorial approach (T-cell therapy and
checkpoint control) to improve clinical responses. Work on the Immunotherapy Platform, led by program
members Drs. Allison, Padmanee Sharma, and Hwu and funded by the cancer center, spans multiple aims and
serves as a mechanism to foster iterative cycles of translation between basic and clinical work by providing
immune monitoring of patient samples and driving new preclinical and clinical studies by generating mechanistic
data to inform rational design of new drug combinations. As of May 1, 2018, 3,434 patients have been enrolled
across 118 different clinical trials. Annual direct peer-reviewed funding for the Immunology Program is $6.4M,
with $1.9M (30%) from NCI grants and $4.5M (70%) from other peer-reviewed sources. Since the last
submission, the program has produced 464 published papers: 184 (40%) are intraprogrammatic collaborations,
250 (54%) are interprogrammatic collaborations, and 278 (60%) are external collaborations. Sixty-five percent
of articles appeared in journals with IF >5, and 31% appeared in journals with IF >10, including N Engl J Med,
Nature, Cell, Science, Cancer Discov, Immunity, and Proc Natl Acad Sci USA. Program members use all 14
shared resources. Notable accomplishments during the last grant period included the demonstration that anti-
CTLA-4 and anti-PD-1 therapies act on distinct T-cell populations, providing an explanation for the benefit
achieved by combined therapy, and discovery of a positive correlation between gut microbiome diversity and
response to immune checkpoint blockade therapy that is transferred along with fecal transplants. See the
Program Highlights for other noteworthy accomplishments.

Grant Number: 5P30CA016672-49
NIH Institute/Center: NIH
Principal Investigator: JAMES ALLISON