Personalized Fusion Cell Vaccines to Enhance CAR-T Cell Immunotherapies for Hematological Malignancies

Fusion cell vaccines would enhance CAR-T cell activity by increasing the extent and duration of the activity.

Therapeutics

Project Overview

While CAR-T cell therapies have several advantages, they also possess various challenges, including loss of activity associated with exhaustion, and the emergence of antigen negative variants.
Fusion cell (FC) vaccines, in contrast, activate T cells by presenting a range of tumor-associated antigens in the context of the dendritic cell (DC) machinery but they also come with limitations.
To overcome these limitations, Dana-Farber researchers and their colleagues have created a novel cancer therapeutic using a fused dendritic cell/tumor cell vaccine that can be used with CAR T therapy.
Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new oncology therapeutics.

Technology

The development of chimeric antigen receptor (CAR) T cell therapy has been highly effective in the treatment of hematological malignancies, including CD19-positive B cell malignancies, over the past two decades. CAR-T cell therapy uses T cells engineered to express a synthetic receptor protein to target specific tumor cell surface antigens that are overexpressed. CAR-T cells have also begun to show efficacy in the treatment of other hematological malignancies, such as B-cell maturation antigen (BCMA)-expressing multiple myeloma (MM).

While CAR-T cell therapies have several advantages, they also possess various challenges, including loss of activity associated with exhaustion, and the emergence of antigen negative variants.

Fusion cell (FC) vaccines, in contrast, activate T cells by presenting a range of tumor associated antigens in the context of the dendritic cell (DC) machinery. Despite having multiple advantages, FC vaccines also come with limitations, such as applications primarily in low tumor burden. Although CAR-T cell therapies and FC vaccines are substantial improvements in available cancer treatment options, ways to overcome their associated limitations are necessary.

The present invention by Dr. Donald Kufe at Dana-Farber, in collaboration with Dr. David Avigan and Dr. Jacalyn Rosenblatt at Beth Israel Deaconess Medical Center, involves the development of a novel cancer therapeutic. A DC is initially fused with a tumor cell to obtain an FC. The FC is then contacted with a T cell to obtain an educated T cell, which is then combined with an established anti-cancer therapy (e.g., CAR-T cell therapy) to create the novel cancer therapeutic.

This approach is beneficial because FC vaccines can not only activate CAR-T cells, but also prolong activation by maintaining memory by inducing CD4+ T cells, as well as prevent the development of antigen negative variants. The use of FC vaccines to enhance CAR-T cell activity would be accomplished by using (i) personalized tumor cell/DC fusions and/or, (ii) personalized molecular FC vaccines. The procedure would involve administering the FC vaccines before, during, and/or after infusion of the CAR-T cells. The vaccine would be modified to stimulate responses to antigens specifically targeted by the CAR-T, including CD19 and BCMA. FC vaccines would enhance CAR-T cell activity by increasing the extent and duration of the activity in settings of established CAR-T cell effectiveness as well as in settings of limited efficacy.

Team Members: Donald W. Kufe, MD, Jacalyn Rosenblatt, MD

Applications

Personalized FC vaccines to enhance the efficacy of CAR-T cell immunotherapy.

Opportunities

Dana-Farber Cancer Institute is looking for the right partner with an interest in licensing these assets for further development into new oncology therapeutics.

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