Intravenous Administration Could Be Key to Peptide-Based Cancer Vaccines

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Administration of vaccines via the unconventional intravenous route conferred greater antitumor activity in mice than the traditional subcutaneous route.
Administration of vaccines via the unconventional intravenous route conferred greater antitumor activity in mice than the traditional subcutaneous route.

In mice, administration of peptide-based vaccines, along with poly-ICLC adjuvant, via the unconventional intravenous route conferred higher cytotoxic T-lymphocyte (CTL) responses and greater antitumor activity than the conventional subcutaneous route.1 The study results were published online January 2, 2019, in Cancer Immunology, Immunotherapy.

Study researchers showed in mice that intravenous administration of peptide-based vaccines were more efficient at expanding adoptively transferred antigen-specific CTLs than vaccines delivered subcutaneously and even intramuscularly. Furthermore, they demonstrated that expansion of CTLs required a peptide antigen.

Long peptides have been described as more effective in vaccines than small, minimal peptides, and experiments in mice revealed that amphiphilic palmitoylated peptides were more immunogenic and “considerably” more efficient than long peptides at expanding CTLs. Study researchers further showed that intravenous administration of amphiphilic pam peptides or long peptides were more effective than subcutaneous administration in mice. Systemic administration was shown to induce interaction between antigen-presenting cells and T cells at multiple sites.

In mice with melanomas, adoptive transfer of CTLs followed by vaccination was shown to differ by route of administration. Subcutaneous administration slowed tumor growth, but intravenous administration of the vaccine was more effective, and the difference in antitumor activity was associated with the extent of CTL responses produced in the mice.

“The overall results show that the systemic administration of palmitoylated peptide-based vaccines is essential to recruit, activate, and expand low number of antigen-specific cells and exert maximal antitumor effects,” the study authors wrote.

Reference

  1. Sultan H, Kumai T, Nagato T, Wu J, Salazar AM, and Celis E. The route of administration dictates the immunogenicity of peptide-based cancer vaccines in mice [published online January 2, 2019]. Cancer Immunol Immunother. doi: 10.1007/s00262-018-02294-5

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