WT1 Targeted T-Cell Program (WT1-CTL)

MULTIPLE MYELOMA AND PCL

Multiple Myeloma, a malignancy of the plasma cell, is the second most common cancer of the blood-forming system with approximately 26,850 new cases and 11,240 deaths estimated in the US for 2015. Of those new cases, approximately two to four percent are PCL, with an aggressive clinical course. In 2011, it was reported in the journal Blood that the prognosis of PCL is poor with a median survival of seven to eleven months and that survival is even shorter two to seven months, when PCL occurs in the context of refractory or relapsing Mutiple Myeloma.

MECHANISM OF ACTION

WT1 is normally expressed during fetal development and can be found at very low levels in the genitourinary tract after birth, but becomes reactivated and expressed in many malignancies. WT1-CTLs provide the patient with T-cells designed to recognize and target the abnormal cells that overexpress WT1.

PUBLICATIONS AND ORAL PRESENTATIONS

Doubrovina E, Carpenter T, Pankov D, Selvakumar A, Hasan A, O’Reilly RJ. Mapping of novel peptides of WT-1 and presenting HLA alleles that induce epitope-specific HLA-restricted T cells with cytotoxic activity against WT-1(+) leukemias. Blood. 2012 Aug 23;120(8):1633-46. doi: 10.1182/blood-2011-11-394619. Epub 2012 May 23 (Citation)

Tyler EM, Jungbluth AA, O’Reilly RJ, Koehne G. WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions. Blood. 2013 Jan 10; 121(2):308-17. doi: 10.1182/blood-2012-06-435040. Epub 2012 Nov 16 (Citation)

Koehne G, Kosuri S, Doubrovina E, Dao T, Scott A, Jungbluth A, O’Reilly RJ. Wilms’ Tumor 1 Protein Is Highly Expressed on Malignant Plasma Cells and Provides a Novel Target for Immunotherapeutic Approaches. Abstract 98 presented December 5, 2015 at the American Society of Hematology Annual Meeting 2015. (Citation)