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Pachynski RK, Morishima C, Szmulewitz R, et al. IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2021;9(8)doi: 10.1136/jitc-2021-002903.
Pachynski, R. K., Morishima, C., Szmulewitz, R., Harshman, L., Appleman, L., Monk, P., Bitting, R. L., Kucuk, O., Millard, F., Seigne, J. D., Fling, S. P., Maecker, H. T., Duault, C., Ramchurren, N., Hess, B., D'Amico, L., Lacroix, A., Kaiser, J. C., Morre, M., Grégoire, A., Cheever, M., Yu, E. Y., & Fong, L. (2021). IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC). Journal for immunotherapy of cancer, 9(8), . https://doi.org/10.1136/jitc-2021-002903
Pachynski, Russell K, et al. "IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC)." Journal for immunotherapy of cancer vol. 9,8 (2021). doi: https://doi.org/10.1136/jitc-2021-002903
Pachynski RK, Morishima C, Szmulewitz R, Harshman L, Appleman L, Monk P, Bitting RL, Kucuk O, Millard F, Seigne JD, Fling SP, Maecker HT, Duault C, Ramchurren N, Hess B, D'Amico L, Lacroix A, Kaiser JC, Morre M, Grégoire A, Cheever M, Yu EY, Fong L. IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC). J Immunother Cancer. 2021 Aug;9(8). doi: 10.1136/jitc-2021-002903. PMID: 34452927; PMCID: PMC8404457.
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J Immunother Cancer. 2021 Aug;9(8). doi: 10.1136/jitc-2021-002903.

IL-7 expands lymphocyte populations and enhances immune responses to sipuleucel-T in patients with metastatic castration-resistant prostate cancer (mCRPC).

Journal for immunotherapy of cancer

Russell K Pachynski, Chihiro Morishima, Russell Szmulewitz, Lauren Harshman, Leonard Appleman, Paul Monk, Rhonda L Bitting, Omer Kucuk, Frederick Millard, John D Seigne, Steven P Fling, Holden T Maecker, Caroline Duault, Nirasha Ramchurren, Bruce Hess, Leonard D'Amico, Andreanne Lacroix, Judith C Kaiser, Michel Morre, Anne Grégoire, Martin Cheever, Evan Y Yu, Lawrence Fong

Affiliations

  1. Department of Medicine, Washington University School of Medicine, St Louis, MO, USA [email protected] [email protected].
  2. University of Washington, Seattle, Washington, USA.
  3. University of Chicago Pritzker School of Medicine, Chicago, Illinois, USA.
  4. Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA.
  5. *Current affiliation: Surface Oncology, Cambridge, MA, USA.
  6. UPMC, Pittsburgh, Pennsylvania, USA.
  7. Ohio State University James Cancer Hospital, Columbus, Ohio, USA.
  8. Wake Forest Baptist Health, Winston-Salem, North Carolina, USA.
  9. Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, Georgia, USA.
  10. University of California San Diego, La Jolla, California, USA.
  11. Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
  12. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
  13. Institute for Immunity, Transplantation and Infection, Stanford University, Stanford, CA, USA.
  14. RevImmune, Paris, France.
  15. University of California San Francisco, San Francisco, California, USA [email protected] [email protected].

PMID: 34452927 PMCID: PMC8404457 DOI: 10.1136/jitc-2021-002903

Abstract

BACKGROUND: Sipuleucel-T (sip-T) is a Food and Drug Administration (FDA)-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer (mCRPC). We hypothesized that combining sip-T with interleukin (IL)-7, a homeostatic cytokine that enhances both B and T cell development and proliferation, would augment and prolong antigen-specific immune responses against both PA2024 (the immunogen for sip-T) and prostatic acid phosphatase (PAP).

METHODS: Fifty-four patients with mCRPC treated with sip-T were subsequently enrolled and randomized 1:1 into observation (n=26) or IL-7 (n=28) arms of a phase II clinical trial (NCT01881867). Recombinant human (rh) IL-7 (CYT107) was given weekly×4. Immune responses were evaluated using flow cytometry, mass cytometry (CyTOF), interferon (IFN)-γ ELISpot,

RESULTS: Treatment with rhIL-7 was well tolerated. For the rhIL-7-treated, but not observation group, statistically significant lymphocyte subset expansion was found, with 2.3-2.6-fold increases in CD4+T, CD8+T, and CD56

CONCLUSIONS: Treatment with rhIL-7 led to a significant expansion of CD4+ and CD8+ T cells, and CD56

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Keywords: T-lymphocytes; clinical trials as topic; cytokines; immunotherapy; prostatic neoplasms

Conflict of interest statement

Competing interests: MM and AG are employees of RevImmune who provided CYT107 for this trial. LF, RKP and PM served in advisory/consulting roles for Dendreon. EYY has received grant funding from Dendr

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