Pin Wang, Ph.D.

A Professor of Chemical and Biomedical Engineering in USC’s Viterbi School of Engineering, Dr. Pin Wang leads a team focused on the emerging field of “immunobioengineering”. The aim of his group’s work is to employ engineering tools and principles to quantitatively understand the immune system in health and disease, and to develop novel immunotherapies by precisely modulating disease-specific immune responses.

Abstract: Chimeric antigen receptors (CARs) are engineered artificial receptors composed of both target-recognition and T-cell activation functions. Once expressed in T lymphocytes, CARs can direct T cells to recognize tumor cells and mediate killing to eradicate the cancer. This type of “living drug” resulted in substantial and durable responses in a subset of patients with B cell malignancies treated with T cells engineered to express a CAR that targets the B cell-specific CD19 molecule. However, attempts to utilize CAR therapies for treatment of solid tumors have been less promising. In this talk, I will begin to present our own clinical experience on the CAR-T therapy for treating B cell malignancies and how costimulatory domains and conditions of cell manufacturing impact in vivo behaviors of CAR-T cells in patients. I will then present a series of strategies undertaken in my laboratory to confront the challenge of CAR-T therapy for solid tumors. One key example is the exploitation of nanoparticle formulation for delivering A2A adenosine receptor antagonists with the aim to modulating tumor microenvironment (TME). We found that small molecular inhibitors can be delivered to the TME by nanoparticles and can efficiently block adenosine signaling. Such a blockade can disrupt adenosine-mediated immunosuppression in the TME and create favorable conditions for infused CAR-T cells to overcome physical barriers and actively infiltrate into the tumor milieu. In addition, CAR-T cells can maintain their biological functions under this blocked environment and are more efficient to mediate antitumor immune responses.

Yvonne Chen, Ph.D.

Dr. Yvonne Chen is an Associate Professor of Microbiology, Immunology and Molecular Genetics at UCLA, as well as a Co-Director of the university’s Comprehensive Cancer Center Tumor Immunology Program. Her current research involves the development of next-generation CAR-T cells with enhanced specificity, reduced toxicity, and the ability to overcome tumor-associated immunosuppression.

Abstract: Engineering Next-Generation T Cells for Cancer Immunotherapy

The adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has demonstrated clinical efficacy in the treatment of advanced cancers, with anti-CD19 CAR-T cells achieving up to 90% complete remission among patients with relapsed B-cell malignancies. However, challenges such as antigen escape and immunosuppression limit the long-term efficacy of adoptive T-cell therapy. Here, I will discuss the development of next-generation T cells that can target multiple cancer antigens and resist immunosuppression, thereby increasing the robustness of therapeutic T cells against tumor defense mechanisms. Specifically, I will discuss the development of multi-input receptors and T cells that can interrogate intracellular antigens. I will also discuss the engineering of T cells that can effectively convert TGF-beta from a potent immunosuppressive cytokine into a T-cell stimulant. This presentation will highlight the potential of synthetic biology in generating novel mammalian cell systems with multifunctional outputs for therapeutic applications.

Paula Cannon, Ph.D.

As an Associate Professor of Molecular Microbiology and Immunology at USC’s Keck School of Medicine, Dr. Paula Cannon leads a research team in studying viruses, stem cells and gene therapies. Although the main focus of Dr. Cannon’s group is to develop HIV therapies, she also studies highly pathogenic hemorrhagic fever viruses, including Ebola and Lassa fever viruses.

Abstract: Genome Editing versus HIV

HIV replication can be successfully suppressed in an infected individual by combination antiretroviral therapies (ART), but these treatments do not result in a cure. Therefore, new approaches are being considered for an HIV cure including gene, cell and immune therapies. These include recently developed sequence-specific DNA editing tools such as CRISPR/Cas9. I will discuss ways in which genome editing is being applied to the challenge of HIV cure, including: (1) creating HIV-resistant cells by disabling the non-essential CCR5 co-receptor gene; (2) boosting or artificially redirecting immune responses against infected cells; (3) creating in vivo cellular factories to secrete anti-HIV factors; and (4) targeting integrated HIV genomes themselves to disable the reservoir of latent HIV genomes that persist despite ART. The first three approaches have the advantage of being amenable to ex vivo cell engineering, the capabilities for which have greatly advanced in recent years. Cells to be engineered include CD4 T cells as the major targets of HIV infection, specific subsets of the immune system such as CD8 T cells or B cells, and the precursor hematopoietic stem cells (HSC) that give rise to all such cells. Strategies targeting the HIV genome itself, however, will require the development of appropriate in vivo delivery methods that can find the “needle in the haystack” that an integrated latent HIV genome represents. In this talk I will highlight progress in these general approaches and describe work from my own lab to enhance and exploit genome editing of hematopoietic cells to target HIV.