Immunology

The Immunology (IMM) Program defines the mechanisms by which tumors evade rejection by the immune system and develops strategies to thwart them. Key to the Program's success is the close integration of IMM clinical, translational, and basic scientists that facilitates rapid progression of novel immunotherapies from the bench to bedside. 

The Specific Aims are: 

Aim 1: Advance and translate T-cell therapies for solid tumors and hematologic malignancies.
The goals of this aim are to bring laboratory and pre-clinical studies to the bedside as novel investigator-initiated clinical trials. Specific areas of focus include: (1) delivery of adoptive T cell immunotherapy using ex vivo expanded tumor-infiltrating lymphocytes and genetically modified immune effector cells; (2) developing mechanistic strategies to improve adoptive cell therapy; (3) restoring and/or improving the potency of tumor-specific responses of immune checkpoint inhibitors, histone deacetylase inhibitors (HDACi), and vaccination; and (4) defining gene expression signatures of immunotherapy responders. MCC support of efforts of IMM members includes: (i) the Immunotherapy Working Group that conceives interventional trials; (ii) a state-of-the-art, Good Manufacturing Practice-compliant, Cellular Therapy Core (CTC); and (iii) the interdisciplinary Immune and Cellular Therapy clinical service that delivers therapy. These clinical trials galvanize the IMM Program into a cohesive unit that is driven to provide highly effective, innovative and safe immunotherapies for cancer patients.

Aim 2: Define molecular and cellular mechanisms to exploit innate and adaptive immunity against cancer.
The goals of this aim are to discover and develop molecular and cellular approaches to harness the immune system. Collaborative studies by the IMM Program members have led to several novel findings in this research arena. Here the specific focus of IMM members includes T-cell recruitment and suppression, natural killer (NK) cell control, myeloid-derived suppressor cells (MDSC) expansion, and the ability of HDACi to modulate immune responses. The research coming from these efforts has led to several innovative cellular and small molecule approaches to interrupt these immune processes, which have been translated into clinical trials.

Aim 3: Prevent graft-versus-host disease (GVHD) while sparing graft-versus-leukemia responses after hematopoietic cell transplantation (HCT).
The goals of this aim are to address unmet needs in human allogeneic-HCT, to prevent GVHD while preserving the transplant immunotherapy potency against leukemia and other blood cancers. The IMM Program has made a significant impact in this field, including the discovery that Th17 cells have central roles in provoking GVHD severity and in the response to standard GVHD therapy. The current focus of this research is to translate these findings for GVHD prevention by either favoring emergence of Treg or blocking Th1 and Th17 differentiation, while sparing cytotoxic T cell responses against the tumor cells. The approaches to prevent GVHD include: (1) adoptive transfer of donor Tregs specific against host minor-histocompatibility antigens (miHAs); (2) targeting the common IL-12/IL-23 p40 receptor chain; (3) targeting JAK2 or STAT3; and (4) defining gene expression signatures associated with operational tolerance following allogeneic HCT.

Immunology Department Members
 
Program Leaders:
Claudio Anasetti, MD
Jose Conejo-Garcia, PhD 

Members:
Daniel Abate-Daga, PhD
Claudio Anasetti, MD
Scott J. Antonia, MD, PhD
Amer A. Beg, PhD
Brian C. Betts, MD
Jason B. Brayer, MD, PhD
Pearlie K. Burnette, PharmD, PhD
Benjamin C. Creelan, MD
Brian Czerniecki, MD, PhD
Marco L. Davila, MD, PhD
Julie Yin Djeu, PhD
Tomar Ghansah, PhD
Jongphil Kim, PhD
Frederick Locke, MD
Joseph Markowitz, MD, PhD
Jane L. Messina, MD
James Mulé, I-PhD
Joseph Pidala, MD, PhD
Shari A. Pilon-Thomas, PhD
Javier Pinilla-Ibarz, MD, PhD
Brian Ruffell, PhD
Amod Sarnaik, MD
Hatem Soliman, MD
Vernon K. Sondak, MD
Sheng Wei, MD
Kenneth L. Wright, PhD