Mission

Our mission is to advance innovative science that coalesces the fields of immunotherapy, immune signaling, and radiation with the goal of translating impactful findings to the clinic. To accomplish this, we prioritize questions and approaches with paradigm-shifting potential. Partnering with The Mark Foundation for Cancer Research enables us to pursue this mission by leveraging the expertise and collaborative relationships of a world-class team of scientists at the University of Pennsylvania. The Center director is Andy Minn, MD, PhD.

Motivation

Immunotherapy has revolutionized cancer treatment and motivates us to build on these successes by broadening its impact across more patients and more cancer types. Many widely used cancer therapies such as radiation can influence the anti-tumor immune response and synergize with immunotherapy. These synergistic effects tap into immune signaling pathways widely expressed by human cancers but are typically understood in the context of pathogen infection (such as viruses and bacteria). We believe understanding the role that these key immune signaling pathways play in cancer offers a promising and imminently deployable strategy to improve immunotherapy.

Vision

We envision that effective immunotherapy approaches can be developed by understanding how immune signaling pathways commonly activated by pathogens can also be modulated by cancer and cancer therapies like radiation. Our vision is to clinically translate this biology to improve immunotherapy by identifying therapeutic targets, using next-generation radiation modalities, and engineering novel chimeric antigen receptor (CAR) T cells that can modulate these immune signaling pathways in the tumor.

Checkpoint blockade

Blocking the function of inhibitory receptors found on immune cells (immune checkpoint receptors) has changed the landscape of cancer treatment and may represent a therapeutic cornerstone for some cancer types. Unfortunately, resistance and relapse are common. We seek to understand major mechanisms of therapeutic resistance that are coordinated by both cancer cells and T cells.

CAR T cells

Another revolutionary cancer immunotherapy is chimeric antigen receptor (CAR) T cells. Our goal is to engineer CAR T cells to not only improve their function but also to enable them to favorably recruit endogenous immune cells to participate in tumor killing.

Innate immunity

Optimal immune responses require proper activation of innate immune cells to either facilitate or complement adaptive immune function. We seek to understand the contribution of select innate immune populations to immunotherapy response and how to more effectively activate them.

Interferon and PRRs

The interferon and pattern recognition receptor pathways (PRRs) are typically associated with pathogen infection, yet are pervasively expressed across human cancers. Moreover, common cancer therapies such as radiation can also activate these pathways. A major goal is to understand the function and regulation of these pathways in cancer cells and associated immune cells.

Inflammatory signaling

Cancer has been described as a “wound that does not heal”. This description represents the ability of cancer cells to disrupt the homeostatic properties of inflammatory signaling that drive tumor growth, promote immune evasion, and suppress cell death. We seek to understand the critical regulators of inflammatory signaling that cancer cells exploit.

Cancer-immune cross-talk

In the tumor microenvironment, cancer cells communicate with immune cells both locally and systemically. We are identifying how perturbations in cancer cells are propagated back-and-forth with immune populations to influence immunotherapy response.

FLASH radiation

Unlike conventional radiation therapy that is typically delivered to patients over weeks, FLASH radiation can deliver an ultra-concentrated dose in less than one second. A major objective is to understand the biology of this next-generation radiation modality with the goal of facilitating its clinical translation.

Immune effects

Conventional radiation can impact the immune system and improve immunotherapy by activating innate immune signaling pathways. We seek to characterize and investigate the immunogenic effects of FLASH radiation.

Normal tissue effects

FLASH radiation has approximately similar anti-tumor efficacy compared to conventional radiation but is associated with significantly less normal tissue toxicity. Center scientists are working together to investigate the biology behind this normal tissue-sparing effect.

Our Team

To successfully tackle the questions that will fulfill the mission and vision of the Center, we have assembled a highly complementary and outstanding team of scientist from Penn. This team spans multiple disciplines that include immunology, virology, cancer biology, inflammatory and innate immune signaling, DNA repair and damage response, radiation biology, medical and particle physics, CRISPR and mouse genetics, functional and genetic screening, and computational biology and statistics. Importantly, the team is comprised of junior and senior scientists who have successfully worked together and represent the exceptionally collaborative environment at Penn.

News, Twitter, and LitBot

Twitter

Immunotherapy Literature Bot

Automated literature searches of select journals and BioRxiv.