Michel Sadelain, MD, PhD

Michel Sadelain, MD, PhD
Memorial Sloan Kettering Cancer Center (New York, NY)
 

Year Funded:
2004

Focus:
Malignant Pleural Mesothelioma

Targeting leukemia and lymphoma with CD19-specific T cells co-stimulated by CD28 and lnterleukln-15

This clinical translational proposal aimed to assess the therapeutic potential of genetically targeted T cells in the treatment of leukemia and lymphoma. The introduction of genes that code for tumor-specific receptors into T lymphocytes, which are cells of the immune system that mediate tumor elimination, was a novel approach to cancer therapy.

Dr. Sadelain demonstrated that human peripheral blood T cells could be effectively redirected to recognize the CO19 antigen and eradicate established, systemic human B cell tumors borne by immunodeficient mice, This was the first publication showing that genetically modified human T cells can induce durable remissions in an in vivo setting.

Importantly, he found that T cell stimulation with the cytokine lnterleukln-15, but not the widely used lnterteukin-2, is critical for sustaining the therapeutic activity of infused CO19-spedflc T cells. Having examined the nature of the signals required by the T cells for their own survival and sustained functionality, Dr. Sadelain designed improved antigen receptors that provide both activating and co-stimulatory signals to the tumor-targeted T cell.

The specific alms of the 2004 application included:

  1. Demonstrating the therapeutic efficacy of leukemia and lymphoma patients’ cos+ T lymphocytes transduced with the 19/28z receptor In tumor-bearing mice
  2. Establishing clinical conditions for patient T cell purification, transduction and expansion, for review by the FDA
  3. Investigating, in a phase I clinical trial In patients with relapsed B cell leukemias, the safety, persistence and therapeutic efficacy of autologous IL15-actlvated CDS+ T cells that express 19/2Sz

Academic Profile

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Michel Sadelain, MD, PhD
Stephen and Barbara Friedman Chair
Director, Center for Cell Engineering
Memorial Sloan Kettering Cancer Center
1275 York Avenue
New York, NY 10065