“One of the challenges in developing anticancer vaccines is to identify antigens that are present only on cancer cells, but not on normal cells,” Dr Hutchins said. “Strategies for myeloma vaccine development include in vitro expansion of patient-derived antigen presenting cells (ie dendritic cells), fusion of cancer cells with dendritic cells, isolating and reproducing antigens from myeloma cells in the laboratory, and manufacturing synthetic myeloma-specific peptide vaccines.”

One recently-reported candidate peptide vaccine developed by researchers in China, for example, combines 2 multiple myeloma–specific targets, multiple myeloma special antigen-1 (MMSA-1) and the Dickkopf-1 Wnt signaling pathway inhibitor 1 protein (DKK1).2

MMSA-1, recently discovered by the authors of the recent study, is strongly associated with myeloma.2,3


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DKK1 regulates osteoblast function and is “highly expressed in the tumor cells of almost all myeloma patients,” the authors reported.

The researchers first confirmed cytotoxic T lymphocyte responses to specific MMSA-1 epitopes in vitro and then engineered a multi-epitope peptide vaccine bearing those epitopes plus DKK1 for testing against multiple myeloma in mice.

“This combined vaccine resulted in more potent anti-myeloma activity compared to single-epitope vaccination in mouse models,” Dr Hutchins noted of the study.

In myeloma-bearing, immune-deficient mice, the combined MMSA-1/DKK1 vaccine improved mouse survival times compared to single-epitope myeloma vaccines, reducing tumor volume and bone loss.

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“The frequencies of CD4+ and CD8+ T cells [were] significantly increased in mouse blood induced by the multi-epitope vaccine, indicating that it inhibits myeloma growth by changing T cell subsets and alleviating immune paralysis,” they wrote.

Much more research is, however, needed. But if additional preclinical tests confirm the promise and safety of this vaccine in lab animals, it might join other candidate myeloma vaccines in human clinical testing.

References

  1. Neri P, Bahlis NJ, Lonial S. New strategies in multiple myeloma: immunotherapy as a novel approach to treat patients with multiple myeloma. Clin Cancer Res. 2016;22(24):5959-65. doi: 10.1158/1078-0432.CCR-16-0184
  2. Lu C, Meng S, Jin Y, et al. A novel multi-epitope vaccine from MMSA-1 and DKK1 for multiple myeloma immunotherapy. Br J Haematol. 2017 May 16. doi: 10.1111/bjh.14686 [Epub ahead of print]
  3. Meng S, Lu C, Zhang W, et al. MMSA-1 expression pattern in multiple myeloma and its clinical significance. Clin Exp Med. 2016;16(4):599-609.