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Boosting humoral and cellular immunity to pneumococcus by vaccination before and just after autologous transplant for myeloma

Bone Marrow Transplantation volume 51, pages 291–294 (2016)Cite this article

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High-dose chemotherapy and autologous stem cell transplant leads to significant immunodeficiency.1 The standard of care is vaccination against infectious agents beginning 3–12 months after transplant.2 To improve early post-transplant immunity, pre- or post-chemotherapy vaccination strategies were designed to capitalize on immune cell homeostatic proliferation occurring after chemotherapy-induced lymphopenia.3, 4 These strategies induce antibody and T-cell responses against infectious antigens and tumor-associated antigens,4, 5, 6 yet responses are incremental over controls unless additional cellular manipulations, such as ex vivo polyclonal activation of T-cells or dendritic cell-tumor fusions are performed.7, 8 Using a murine model, Brody et al. demonstrated that vaccination before hematopoietic cell collection elicits strong post-transplant CD4+ and CD8+ responses which were potentiated by additional vaccination immediately post transplant, and they named this procedure ‘immunotransplant’.9 Pneumococcal vaccination before stem cell collection was previously tested revealing antibody responses, however early posttransplant vaccination was not performed and T-cell responses were not demonstrated.4 None of these human trials coupled immunization just before standard G-CSF primed unfractionated hematopoietic cell collection with immunization again early post transplant, during the period of homeostatic proliferation.

We hypothesized that immune responses could be generated by vaccination and immunotransplant without ex vivo T-cell expansion. To test this, we conducted a feasibility and biological activity study of Prevnar-13 (PCV-13), a pneumococcal 13-valent conjugate (diphtheria CRM197 protein) vaccination, administered in a novel schedule in conjunction with standard high-dose melphalan chemotherapy (200 mg/m2) and autologous hematopoietic cell transplant for adult patients with multiple myeloma. PCV-13 was administered before G-CSF mobilization and hematopoietic cell collection and again during the lymphopenic period, 7–21 days after transplant. All patients signed informed consent to this Institutional Review Board approved study registered on ClinicalTrials.gov (NCT01852591). Patients were scheduled to receive up to three IM injections of 0.5 mL of PCV-13. Each vaccine contains serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F individually conjugated to a nontoxic variant of diphtheria toxin (CRM197). The three vaccine administrations were scheduled as follows: (1) between 3 and 30 days before the first day of standard G-CSF administration for hematopoietic cell mobilization; (2) between day +7 and +10 after autologous hematopoietic cell infusion (that is, transplant); and (3) between day +21 and +24 after transplant. Vaccine was deferred for platelets <50 000 cells/microL, fever, or systemic inflammatory response syndrome. Adverse events not expected with standard autologous transplant were graded using CTCAE v4.03 following each vaccination to day +90 and assigned by the treating physician as possible, probable or unlikely related to vaccination. Biological endpoints of this study included antibody responses against pneumococcal serotypes and T-cell responses against CRM197.

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References

  1. Guillaume T, Rubinstein DB, Symann M . Immune reconstitution and immunotherapy after autologous hematopoietic stem cell transplantation. Blood 1998; 92: 1471–1490.

    CAS  PubMed  Google Scholar 

  2. Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15: 1143–1238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Dudley ME, Wunderlich JR, Robbins PF, Yang JC, Hwu P, Schwartzentruber DJ et al. Cancer regression and autoimmunity in patients after clonal repopulation with antitumor lymphocytes. Science 2002; 298: 850–854.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Antin JH, Guinan EC, Avigan D, Soiffer RJ, Joyce RM, Martin VJ et al. Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11: 213–222.

    Article  CAS  PubMed  Google Scholar 

  5. Rapoport AP, Aqui NA, Stadtmauer EA, Vogl DT, Fang HB, Cai L et al. Combination immunotherapy using adoptive T-cell transfer and tumor antigen vaccination on the basis of hTERT and survivin after ASCT for myeloma. Blood 2011; 117: 788–797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Hata A, Asanuma H, Rinki M, Sharp M, Wong RM, Blume K et al. Use of an inactivated varicella vaccine in recipients of hematopoietic-cell transplants. N Engl J Med 2002; 347: 26–34.

    Article  PubMed  Google Scholar 

  7. Rapoport AP, Stadtmauer EA, Aqui N, Badros A, Cotte J, Chrisley L et al. Restoration of immunity in lymphopenic individuals with cancer by vaccination and adoptive T-cell transfer. Nat Med 2005; 11: 1230–1237.

    Article  CAS  PubMed  Google Scholar 

  8. Rosenblatt J, Avivi I, Vasir B, Uhl L, Munshi NC, Katz T et al. Vaccination with dendritic cell/tumor fusions following autologous stem cell transplant induces immunologic and clinical responses in multiple myeloma patients. Clin Cancer Res 2013; 19: 3640–3648.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brody JD, Goldstein MJ, Czerwinski DK, Levy R . Immunotransplantation preferentially expands T-effector cells over T-regulatory cells and cures large lymphoma tumors. Blood 2009; 113: 85–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Prevnar 13 prescribing information. http://www.fda.gov/downloads/biologicsbloodvaccines/vaccines/approvedproducts/ucm201669.pdf.

  11. Szu SC, Lee CJ, Parke JC Jr, Schiffman G, Henrichsen J, Austrian R et al. Cross-immunogenicity of pneumococcal group 9 capsular polysaccharides in adult volunteers. Infect Immun 1982; 35: 777–782.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Lendvai N, Cohen AD, Cho HJ . Beyond consolidation: auto-SCT and immunotherapy for plasma cell myeloma. Bone Marrow Transplant 2015; 50: 770–780.

    Article  CAS  PubMed  Google Scholar 

  13. Gattinoni L, Lugli E, Ji Y, Pos Z, Paulos CM, Quigley MF et al. A human memory T cell subset with stem cell-like properties. Nat Med 2011; 17: 1290–1297.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported in part by the Cancer Center Support Grant P30 CA076292 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL, USA

    F L Locke, M Menges, T Nishihori, C Nwoga, M Alsina & C Anasetti

  2. Department of Oncologic Sciences, University of South Florida, Tampa, FL, USA

    F L Locke, T Nishihori, M Alsina & C Anasetti

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  1. F L Locke
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  2. M Menges
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Correspondence to F L Locke.

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Locke, F., Menges, M., Nishihori, T. et al. Boosting humoral and cellular immunity to pneumococcus by vaccination before and just after autologous transplant for myeloma. Bone Marrow Transplant 51, 291–294 (2016). https://doi.org/10.1038/bmt.2015.239

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