Category: Laboratory Research

Cross Campus Collaboration Leads to Potential New Development of Treatment of B-Cell Lymphomas

Researchers at Cornell University announced the development of a second generation of functional, synthetic immune organoids that can be independently controlled by medical researchers. This development has many potential utilities though it hold special promise in the development of treatments for B cell lymphomas. Specifically in testing compounds with the potential to eliminate the malignization of lymphocytes and/or to increase the antibody production capacity of B-cells.

“The synthetic organ is bio-inspired by secondary immune organs like the lymph node or spleen. It is made from gelatin-based biomaterials reinforced with nanoparticles and seeded with cells, and it mimics the anatomical microenvironment of lymphoid tissue. Like a real organ, the organoid converts B cells – which make antibodies that respond to infectious invaders – into germinal centers, which are clusters of B cells that activate, mature and mutate their antibody genes when the body is under attack. Germinal centers are a sign of infection and are not present in healthy immune organs.”

The immune organoid was created in the lab of Dr. Ankur Singh at Cornell University, and resulted from an ongoing collaboration with Dr. Leandro Cerchietti, a research collaborator of the Lymphoma Program at Weill Cornell Medical College, and Dr. Akhilesh Gaharwar of Texas A&M University. This collaboration between Cornell University and Weill Cornell Medical College is known as the P.A.Th pipeline. P.A.Th. was designed to expedite the bench to bedside approach taken by the Lymphoma Program as Weill Cornell Medical College.

For patients with B-cell lymphoma Dr. Singh commented,

“In the long run, we anticipate that the ability to drive immune reaction ex vivo at controllable rates grants us the ability to reproduce immunological events with tunable parameters for better mechanistic understanding of B cell development and generation of B cell tumors, as well as screening and translation of new classes of drugs.” 

Full results for this new discovery were published online in Biomaterials, and will appear in print. Look to this space for further updates on further collaborations between Cornell University and Weill Cornell Medical College.

FDA Grants Breakthrough Therapy Designation to Venetoclax for Patients with Relapsed/Refractory CLL with 17p Deletion

Earlier today the FDA granted the Breakthrough Therapy Designation to venetoclax (ABT-199). Venetoclax was awarded this designation for the treatment of relapsed or refractory CLL in previously treated patients with 17p deletion. Venetoclax is an inhibitor of the B-cell lymphoma-2 (BCL-2) protein.

The Breakthrough Therapy Designation is intended to expedite the development and review of drugs for life-threatening conditions, based on preliminary clinical evidence. A full list of targeted treatments that have received FDA approval for the treatment of lymphoma can be found here.

Currently the Lymphoma Program has several phase 2 trials open to accrual for ABT-199 as a treatment for CLL patients. Dr. Richard Furman is the principal investigator for both trials:

Phase 2 Open-Label Study of the Efficacy and Safety of ABT-199 (GDC-0199) in Chronic Lymphocytic Leukemia Subjects with Relapse or Refractory to B-cell Receptor Signaling Pathway Inhibitor Therapy

Phase 2 Open-Label Study of the Efficacy of ABT-199 in Subjects with Relapsed or Refractory Chronic Lymphocytic Leukemia Harboring the 17p Deletion

A full listing of available CLL trials can be found here. Look to this space for more information regarding developments for the treatment of CLL.

Palbociclib and One Researcher’s Resolve

Palbociclib is a selective CDK4/6 inhibitor approved by the FDA for the treatment of patients with breast cancer. Currently it’s being tested in phase I trials for the treatment of patients with mantle cell lymphoma. The use of palbociclib as a cancer treatment was championed by Selina Chen-Kiang, PhD., professor of Pathology & Laboratory Medicine and Microbiology & Immunology, and a key collaborator with the Lymphoma Program. Palbociclib is currently considered one of the next big things in cancer treatment. But:

“..it’s old news for Selina Chen-Kiang, Ph.D…who has been a cheerleader for palbociclib for the past decade. In fact, her relentless effort helped resurrect the drug after it was shelved by an uninterested pharmaceutical company, and her initial findings inspired the clinical trials that paved the path for its accelerated approval.”    

“Chen-Kiang is renowned for her research in immunology and hematological malignancies. A molecular biologist by training, she first got swept into myeloma and lymphoma research while studying how antibody-secreting plasma cells were generated from B cells. Unlike solid tissue, normal immune cells can be isolated at different stages from mice and humans, making them the perfect model to study her primary passion: cell cycle control of immunity.”

Today Dr. Chen-Kiang’s dogged inquiry into the potential of palbociclib has the potential to help cancer patients. Her resolve exemplifies the bench portion of our bench to bedside approach at the Meyer Cancer Center. Palbociclib is currently undergoing phase I investigator-initiated trials, sponsored by the Cancer Therapy Evaluation Program at the National Cancer Institute at Weill Cornell Medical College. The principle investigator is Dr. Peter Martin. You can listen to him explain explain the benefits of this recently initiated trial: