The National Cancer Institute (NCI) recently renewed funding of City of Hope’s laboratory and translational research efforts to develop improved treatments for Hodgkin and non-Hodgkin lymphoma. The grant extends the NCI’s recognition of City of Hope’s Specialized Program of Research Excellence for lymphoma (Lymphoma SPORE), which the NCI first funded in 2004.

Stephen Forman (Photo by Walter Urie)

“The renewal of our Lymphoma SPORE by the NCI is welcome recognition of the scientific advances happening at City of Hope and how we consistently turn those improvements into better care for cancer patients,” said Michael A. Friedman, M.D., president and chief executive officer of City of Hope and Irell & Manella Cancer Center Director’s Distinguished Chair.

The Lymphoma SPORE renewal continues this research across four projects focusing on various ways to improve lymphoma treatment. It also supports a developmental research program and a career development program to foster the advancement of pilot translational research projects and young investigators focused on lymphoma. The grant’s principal investigator is Stephen J. Forman, M.D., Francis and Kathleen McNamara Distinguished Chair in Hematology and Hematopoietic Cell Transplantation, and it supports integrated collaborations between laboratory and clinical investigators from all programs in the comprehensive cancer center.

CD19 Specific Central Memory T Cell Adoptive Immunotherapy for Non-Hodgkin Lymphoma

Principal investigators: Leslie Popplewell, M.D., Jamie Wagner, Michael Jensen, M.D., Stanley Riddell, M.D., Xiuli Wang, M.D., Ph.D., Christine Brown, Ph.D., and Stephen J. Forman, M.D.

Disease relapse is a concern for non-Hodgkin lymphoma patients, even after an autologous bone marrow transplant, or BMT. Some lymphoma cells survive the intense therapy and can cause a relapse. The T-cell project focuses on developing an immunotherapy using genetically modified T cells that recognize certain molecules on lymphoma cells. The patient receives the T cells in an infusion after BMT to help eradicate any remaining lymphoma cells.

Therapy-related Leukemia Following Autologous Transplantation for Lymphoma

Principal investigators: Ravi Bhatia, M.D., Smita Bhatia, M.D., M.P.H., and Timothy O’Connor, Ph.D.

Autologous BMT to treat a patient’s lymphoma can sometimes lead to the development of a secondary cancer, such as therapy-related myelodysplasia or acute myelogenous leukemia (t-MDS/AML). City of Hope scientists are studying the molecular basis for the development of t-MDS/AML and aim to identify risk factors and biomarkers that might lead clinicians to change a patient’s treatment or take early steps to prevent the disease.

Humanized Anti-CD20-IL2 for the Treatment of CD20-positive Lymphomas

Principal investigators: Andrew Raubitschek, M.D., Ryotaro Nakamura, M.D., and David Colcher, Ph.D.

Patients with non-Hodgkin follicular lymphoma have a high relapse rate and often require many difficult therapies. Researchers at City of Hope are studying a low-toxicity immunotherapy using a protein they engineered called anti-CD20-IL-2. The protein is an immunocytokine and may boost a patient’s own immune system to react against lymphoma cells to help the patient maintain long-term immunologic control over the disease.

Antibody-mediated Nanoparticle Targeting of siRNA for the Treatment of Lymphoma

Principal investigators: Hua Yu, Ph.D., John Rossi, Ph.D., David Colcher, Ph.D., Mark Davis, Ph.D., and Stephen J. Forman, M.D.

City of Hope scientists are developing new treatments that can block specific genes that cancer cells need to survive, but ensuring the therapy gets into the cells to silence the key genes remains a challenge. Researchers now are developing new ways to deliver molecules called siRNAs that will target lymphoma cells and silence genes such as STAT3, which is crucial to cancer cell survival and growth. This approach may pave the way for the development of new siRNA-based treatments for other cancers.

These efforts also receive support from the Tim Nesvig Lymphoma Fellowship and Research Fund.

The NCI established SPORE grants to promote cancer research projects targeting prevention, early detection, diagnosis and treatment of cancers. There are currently 62 active SPOREs in the U.S. City of Hope is one of five centers in the country awarded a Lymphoma SPORE grant.