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Post-transplant Events

Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients

Bone Marrow Transplantation volume 48, pages 269–277 (2013)Cite this article

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Abstract

To enhance the therapeutic index of allogeneic hematopoietic SCT (HSCT), we immunized 10 HLA-matched sibling donors before stem cell collection with recipient-derived clonal myeloma Ig, idiotype (Id), as a tumor antigen, conjugated with keyhole limpet hemocyanin (KLH). Vaccinations were safe in donors and recipients. Donor-derived KLH- and Id-specific humoral and central and effector memory T-cell responses were detectable by day 30 after HSCT and were boosted by post-transplant vaccinations at 3 months in most recipients. One patient died before booster vaccinations. Specifically, after completing treatment, 8/9 myeloma recipients had persistent Id-specific immune responses and 5/9 had improvement in disease status. Although regulatory T cells increased after vaccination, they did not impact immune responses. At a median potential follow-up period of 74 months, 6 patients are alive, the 10 patients have a median PFS of 28.5 months and median OS has not been reached. Our results provide proof of principle that neoantigen and tumor antigen-specific humoral and cellular immunity could be safely induced in HSCT donors and passively transferred to recipients. This general strategy may be used to reduce relapse of malignancies and augment protection against infections after allogeneic HSCT.

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Acknowledgements

This work was supported by the Center for Cancer Research, the National Cancer Institute, the National Institutes of Health; the Leukemia and Lymphoma Society (Specialized Center of Research Grant No. 7262–08 (LWK)); the National Institutes of Health Grant R21 CA123860 (LWK); the Gateway Foundation (LWK); the American Society of Clinical Oncology Career Development Award (SSN); the American Society of Hematology Junior Faculty Scholar Award in Clinical/Translational Research (SSN); the National Institutes of Health Grant K23CA123149 (SSN); and the Doris Duke Charitable Foundation Clinical Scientist Development Award (SSN). The Immune Monitoring Core Facility and the Flow Cytometry Core Facility at the MD Anderson Cancer Center are supported by the Cancer Center Support Grant CA16672 (National Institutes of Health).

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Author notes

  1. M Foglietta, S S Neelapu and M R Bishop: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Lymphoma and Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Foglietta, S S Neelapu, L W Kwak, Y Jiang, D Nattamai & S-T Lee

  2. Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    M Foglietta, S S Neelapu, L W Kwak, Y Jiang, D Nattamai, S-T Lee, L M Vence, L Radvanyi & K C Dwyer

  3. Experimental Transplantation and Immunology Branch, National Cancer Institute/NIH, Bethesda, MD, USA

    D H Fowler, C Sportes, R E Gress, R N K Bryant & M R Bishop

  4. Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Rockville, MD, USA

    S M Steinberg

  5. Department of Melanoma Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    L M Vence & L Radvanyi

  6. Department of Stem Cell Transplantation and Cellular Therapy, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    K C Dwyer & M H Qazilbash

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  1. M Foglietta
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Correspondence to L W Kwak.

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Foglietta, M., Neelapu, S., Kwak, L. et al. Neoantigen and tumor antigen-specific immunity transferred from immunized donors is detectable early after allogeneic transplantation in myeloma patients. Bone Marrow Transplant 48, 269–277 (2013). https://doi.org/10.1038/bmt.2012.132

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