At the Ruella Lab, we are dedicated to transforming the treatment of lymphoid malignancies through cutting-edge cellular immunotherapy.
At the Ruella Lab, we are dedicated to transforming the treatment of lymphoid malignancies through cutting-edge cellular immunotherapy.
At the Ruella Lab, we are dedicated to transforming the treatment of lymphoid malignancies through cutting-edge cellular immunotherapy. Our research spans the full spectrum from basic science to translational discovery to early-phase clinical trials, with a singular mission: to improve outcomes for patients with lymphoma, leukemia, myeloma and cancer.
A hallmark of our program is its deeply translational nature. We systematically biobank tumor and blood samples from patients treated with commercial CAR T-cell therapies and bispecific antibodies, enabling us to study real-world responses, resistance mechanisms, and toxicities at an unprecedented level of detail. This rich clinical resource fuels our basic and preclinical research and drives the design of next-generation therapies.
We have made pioneering contributions to the understanding of how tumors escape CAR T-cell therapy, including the first report of a leukemic cell acquiring a CAR gene, the discovery of apoptosis pathway defects conferring resistance, and the role of the gut microbiome in influencing treatment efficacy. We have also developed innovative solutions—such as engineered CARs that resist venetoclax-induced apoptosis or target novel CD19 epitopes—and brought these concepts into early human trials.
Our current research continues to break new ground. We are investigating CD5 and BTLA as novel immune checkpoints, developing CAR T cells that selectively target malignant clones while sparing normal B cells, and exploring how diet, antibiotics, and the epigenome can modulate immune responses. Our preclinical models—including animal and patient-derived systems—are central to these efforts and have led to the translation of multiple therapeutic concepts to the clinic.
Through collaborations with clinicians and scientists at Penn and beyond, we harness the power of next-generation sequencing, proteomics, metabolomics, and spatial transcriptomics to uncover the complex interplay between tumors and the immune system.
Ultimately, the Ruella Lab strives to transform scientific insights into curative therapies. Our work has not only shaped the field of immunotherapy but continues to redefine what is possible for patients with otherwise intractable blood cancers.
Here is an overview of our past and current research:
The role of apoptosis in both tumor and CAR T cells: In 2022, we showed how BCL-2 orchestrates responses to CART19 in lymphoma and demonstrated that targeting BCL-2 in both tumor and T cells enhances efficacy (Lee YG, Cancer Discov, 2022). Previously, we identified the extrinsic apoptosis—or “death receptor”—pathway as a critical node for CART19 resistance in B-ALL, confirmed by two clinical trials (Singh N, Cancer Discov, 2020).
The role of apoptosis in both tumor and CAR T cells: In 2022, we showed how BCL-2 orchestrates responses to CART19 in lymphoma and demonstrated that targeting BCL-2 in both tumor and T cells enhances efficacy (Lee YG, Cancer Discov, 2022). Previously, we identified the extrinsic apoptosis—or “death receptor”—pathway as a critical node for CART19 resistance in B-ALL, confirmed by two clinical trials (Singh N, Cancer Discov, 2020).
CAR T cells for T-cell malignancies: We developed a novel CD5-deleted anti-CD5 CAR T-cell therapy with enhanced efficacy (Patel RP, Sci Immunol, 2024), leading to the formation of Vittoria Biotherapeutics and a phase I trial (Senza5 CART5). We are also advancing anti-CD2 CAR T-cell therapies (Angelos M, ASH 2023, #885).
Secondary primary malignancies (SPMs): In response to an FDA safety alert, we were the first to characterize the incidence and nature of SPMs, including CAR-negative T-cell lymphomas, in patients treated with commercial CAR T-cell therapies (Ghilardi G, Nat Med, 2024).
Secondary primary malignancies (SPMs): In response to an FDA safety alert, we were the first to characterize the incidence and nature of SPMs, including CAR-negative T-cell lymphomas, in patients treated with commercial CAR T-cell therapies (Ghilardi G, Nat Med, 2024).
Perelman Center for Advance Medicine
3400 Civic Center Boulevard
South Tower, 8th Floor, Bay 321
Philadelphia, PA 19104
© The Trustees of the University of Pennsylvania
Perelman Center for Advance Medicine
3400 Civic Center Boulevard
South Tower, 8th Floor, Bay 321
Philadelphia, PA 19104
© The Trustees of the University of Pennsylvania