Description of Research Expertise

The Powell Lab is actively investigating the application of immune-based therapy for cancer. Building on interrogations in basic T cell biology in the lab, true bench-to-bedside translational immunology is being developed, with a strong focus on T cell-based therapy for cancer.

Adoptive immunotherapy using natural tumor-reactive T cells has emerged as a promising approach for the treatment of advanced, refractory solid cancer. One obstacle to successful immunotherapy is the lack of highly avid, tumor-reactive T cells in multiple cancers. One current focus of the Powell lab is to generate/isolate high avidity, tumor-reactive T cells from heterogenous tumor infiltrating lymphocyte populations in traditionally "non-immunogenic" cancers utilizing novel culture conditions and T cell capture techniques.

A secondary field of study is the de novo generation of tumor reactive T cells through novel, sophisticated genetic engineering methods. One approach relies on the isolation and cloning of T cell receptors (TCRs) that confer non-reactive T cells with specific and potent immune function following gene transfer via recombinant lentivirus or retrovirus. Another approach relies upon the use of chimeric antigen receptors (CARs) that confer T cells with the MHC-independent specificity of a tumor antigen-specific antibody and potent T cell activity delivered by TCR and costimulatory domains. The Powell Lab employs the CAR approach to test the function of novel costimulatory signals in anti-tumor immunity. Additionally, we pioneered the use of universal immune receptors as a novel platform for CAR screening and for the tailoring of antigen specificity for simultaneous or sequential targeting of target antigens.

Current efforts include the following:

1. Active expansion and characterization of Tumor Infiltrating Lymphocytes (TIL) for use in adoptive cell transfer approaches.
2. The use of lenti- and retroviral vectors to convey high avidity tumor antigen recognition to non-reactive T cells via genetic transfer of tumor-reactive T cell receptors or antibody-based chimeric immune receptors.
3. Development of novel therapeutic strategies to direct T cell effector function to tumor cells, while sparing normal tissues and development of universal immune receptors.
4. Exploring the impact of novel stimulatory domains on T cell phenotype and function in vitro and in xenogeneic models of human cancer.
5. Development of novel cancer vaccine approaches through genetic engineering of cancer cells and pulsing of dendritic cells with autologous tumor lysate, designed to potentiate adoptive immunotherapy.
6. Host immunomodulation through the manipulation of immunoregulatory cells and molecules to potentiate antitumor T cell responses.
7. Preclinical validations; clinical translation and trial support.
8. Biospecimen Processing and Procurement; viable tumor banking.

Lab Personnel and Associates:
- Evripidis Lanitis, Visiting Ph.D. Candidate
- Rachel Lynn, Ph.D. Candidate
- Dr. Degang Song, Post-doctoral Investigator
- Dr. Kasia Urbanska, Post-doctoral Investigator
- Dr. Qunrui Ye, Senior Research Investigator
- Dr. Mathilde Poussin, Ph.D., Lab Manager
- Andrew Best, Cell Processing Technician
- Tom Garrabrant, Flow Cytometry Technician

Description of Clinical Expertise

Clincal Trial Support:
- Clinical Tumor Tissue Processing
- Preclinical validation
- Clinical cell production
- Tumor cell preparation
- Biospecimen processing & banking
- Immune assessment
- Tumor infiltrating lymphocytes (TIL) isolation and expansion
- Assistance for protocols involving adoptive immunotherapy, cancer vaccines and gene therapy