Paul F. Robbins, Ph.D.
Staff Scientist
Head, DNA Sequencing and FACS Cores

Center for Cancer Research
National Cancer Institute

CRC, Rm. 3-5744
Bethesda, MD 20854
301 402-2069

My group is focused primarily on 2 projects: studies of the association of characteristics of tumor reactive T cells administered to patients and clinical response and the generation of high affinity TCRs for the treatment of patients with cancer. These studies have demonstrated that T cell persistence as well as the telomere length of administered T cells is associated with clinical response. Additional studies have indicated that expression of the cellular differntiation marker CD27 is associated with response to therapy. Recent studies have focused on examining the effects of amino acid substitutions in the combining regions of the a and b chains of tumor reactive TCRs have resulted in the identification of high affinity variants of 6 TCRs that lead to enhanced tumor recognition. A modified T cell receptor (TCR) directed against the NY-ESO-1 cancer/testis antigen has now been used to transduce autologous PBMC that were administered to patients with melanoma and synovial cell sarcoma. In this PhaseI/II trial, objective responses were observed in 5 of 11 melanoma patients and 4 of 6 synovial cell sarcoma patients. Pre-clinical studies are now being carried out to develop methods to further enhance the responses of TCR-transduced T cells. Gene cloning studies are also being carried out in an attempt to identify novel antigens recognized by TIL that were asssociated with clinical responses to adoptive immunotherapy.

Areas of Expertise
immunotherapy

My group is focused primarily on 2 projects: studies of the association of characteristics of tumor reactive T cells administered to patients and clinical response and the generation of high affinity TCRs for the treatment of patients with cancer. These studies have demonstrated that T cell persistence as well as the telomere length of administered T cells is associated with clinical response. Additional studies have indicated that expression of the cellular differntiation marker CD27 is associated with response to therapy. Recent studies have focused on examining the effects of amino acid substitutions in the combining regions of the a and b chains of tumor reactive TCRs have resulted in the identification of high affinity variants of 6 TCRs that lead to enhanced tumor recognition. A modified T cell receptor (TCR) directed against the NY-ESO-1 cancer/testis antigen has now been used to transduce autologous PBMC that were administered to patients with melanoma and synovial cell sarcoma. In this PhaseI/II trial, objective responses were observed in 5 of 11 melanoma patients and 4 of 6 synovial cell sarcoma patients. Pre-clinical studies are now being carried out to develop methods to further enhance the responses of TCR-transduced T cells. Gene cloning studies are also being carried out in an attempt to identify novel antigens recognized by TIL that were asssociated with clinical responses to adoptive immunotherapy.

Selected Publications
  1. Lu YC, Yao X, Crystal JS, Li YF, El-Gamil M, Gross C, Davis L, Dudley ME, Yang JC, Samuels Y, Rosenberg SA, Robbins PF.
    Clin. Cancer Res.. 20: 3401-10, 2014. [ Journal Article ]
  2. Aung PP, Liu YC, Ballester LY, Robbins PF, Rosenberg SA, Lee CC.
    Hum. Pathol.. 45: 259-67, 2014. [ Journal Article ]
  3. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA.
    J. Immunother.. 36: 133-51, 2013. [ Journal Article ]
  4. Dudley ME, Gross CA, Somerville RP, Hong Y, Schaub NP, Rosati SF, White DE, Nathan D, Restifo NP, Steinberg SM, Wunderlich JR, Kammula US, Sherry RM, Yang JC, Phan GQ, Hughes MS, Laurencot CM, Rosenberg SA.
    J. Clin. Oncol.. 31: 2152-9, 2013. [ Journal Article ]
  5. Langan RC, Sherry RM, Avital I, Heller T, Henderson C, Holland SM, Freeman AF, Rudloff U.
    J. Gastrointest. Surg.. 17: 1009-14, 2013. [ Journal Article ]
Name Position
Jessica Crystal M.D. Clinical Fellow
Mona El-Gamil Research Biologist
Shawn Farid Research Biologist
Yong Li Research Biologist
Yong-Chen Lu Ph.D. Postdoctoral Fellow (Visiting)
Arnold Mixon Research Biologist
Todd Prickett Ph.D. Research Fellow
Abraham Sachs Summer Student
Katarzyna Trebska-McGowan M.D. Clinical Fellow

Summary

My group is focused primarily on 2 projects: studies of the association of characteristics of tumor reactive T cells administered to patients and clinical response and the generation of high affinity TCRs for the treatment of patients with cancer. These studies have demonstrated that T cell persistence as well as the telomere length of administered T cells is associated with clinical response. Additional studies have indicated that expression of the cellular differntiation marker CD27 is associated with response to therapy. Recent studies have focused on examining the effects of amino acid substitutions in the combining regions of the a and b chains of tumor reactive TCRs have resulted in the identification of high affinity variants of 6 TCRs that lead to enhanced tumor recognition. A modified T cell receptor (TCR) directed against the NY-ESO-1 cancer/testis antigen has now been used to transduce autologous PBMC that were administered to patients with melanoma and synovial cell sarcoma. In this PhaseI/II trial, objective responses were observed in 5 of 11 melanoma patients and 4 of 6 synovial cell sarcoma patients. Pre-clinical studies are now being carried out to develop methods to further enhance the responses of TCR-transduced T cells. Gene cloning studies are also being carried out in an attempt to identify novel antigens recognized by TIL that were asssociated with clinical responses to adoptive immunotherapy.

Areas of Expertise
immunotherapy

Research

My group is focused primarily on 2 projects: studies of the association of characteristics of tumor reactive T cells administered to patients and clinical response and the generation of high affinity TCRs for the treatment of patients with cancer. These studies have demonstrated that T cell persistence as well as the telomere length of administered T cells is associated with clinical response. Additional studies have indicated that expression of the cellular differntiation marker CD27 is associated with response to therapy. Recent studies have focused on examining the effects of amino acid substitutions in the combining regions of the a and b chains of tumor reactive TCRs have resulted in the identification of high affinity variants of 6 TCRs that lead to enhanced tumor recognition. A modified T cell receptor (TCR) directed against the NY-ESO-1 cancer/testis antigen has now been used to transduce autologous PBMC that were administered to patients with melanoma and synovial cell sarcoma. In this PhaseI/II trial, objective responses were observed in 5 of 11 melanoma patients and 4 of 6 synovial cell sarcoma patients. Pre-clinical studies are now being carried out to develop methods to further enhance the responses of TCR-transduced T cells. Gene cloning studies are also being carried out in an attempt to identify novel antigens recognized by TIL that were asssociated with clinical responses to adoptive immunotherapy.

Publications

Selected Publications
  1. Lu YC, Yao X, Crystal JS, Li YF, El-Gamil M, Gross C, Davis L, Dudley ME, Yang JC, Samuels Y, Rosenberg SA, Robbins PF.
    Clin. Cancer Res.. 20: 3401-10, 2014. [ Journal Article ]
  2. Aung PP, Liu YC, Ballester LY, Robbins PF, Rosenberg SA, Lee CC.
    Hum. Pathol.. 45: 259-67, 2014. [ Journal Article ]
  3. Morgan RA, Chinnasamy N, Abate-Daga D, Gros A, Robbins PF, Zheng Z, Dudley ME, Feldman SA, Yang JC, Sherry RM, Phan GQ, Hughes MS, Kammula US, Miller AD, Hessman CJ, Stewart AA, Restifo NP, Quezado MM, Alimchandani M, Rosenberg AZ, Nath A, Wang T, Bielekova B, Wuest SC, Akula N, McMahon FJ, Wilde S, Mosetter B, Schendel DJ, Laurencot CM, Rosenberg SA.
    J. Immunother.. 36: 133-51, 2013. [ Journal Article ]
  4. Dudley ME, Gross CA, Somerville RP, Hong Y, Schaub NP, Rosati SF, White DE, Nathan D, Restifo NP, Steinberg SM, Wunderlich JR, Kammula US, Sherry RM, Yang JC, Phan GQ, Hughes MS, Laurencot CM, Rosenberg SA.
    J. Clin. Oncol.. 31: 2152-9, 2013. [ Journal Article ]
  5. Langan RC, Sherry RM, Avital I, Heller T, Henderson C, Holland SM, Freeman AF, Rudloff U.
    J. Gastrointest. Surg.. 17: 1009-14, 2013. [ Journal Article ]

Team

Name Position
Jessica Crystal M.D. Clinical Fellow
Mona El-Gamil Research Biologist
Shawn Farid Research Biologist
Yong Li Research Biologist
Yong-Chen Lu Ph.D. Postdoctoral Fellow (Visiting)
Arnold Mixon Research Biologist
Todd Prickett Ph.D. Research Fellow
Abraham Sachs Summer Student
Katarzyna Trebska-McGowan M.D. Clinical Fellow