Tumor targeting peptide TMTP1 modified Antigen capture Nano-vaccine combined with chemotherapy and PD-L1 blockade effectively inhibits growth of ovarian cancer

J Nanobiotechnology. 2024 Aug 13;22(1):483. doi: 10.1186/s12951-024-02744-6.

Abstract

The mortality of ovarian cancer (OC) has long been the highest among gynecological malignancies. Although OC is considered to be an immunogenic tumor, the effect of immunotherapy is not satisfactory. The immunosuppressive microenvironment is one reason for this, and the absence of recognized effective antigens for vaccines is another. Chemotherapy, as one of the most commonly used treatment for OC, can produce chemotherapy-associated antigens (CAAs) during treatment and show the effect of in situ vaccine. Herein, we designed an antigen capture nano-vaccine NP-TP1@M-M with tumor targeting peptide TMTP1 and dendritic cell (DC) receptor mannose assembled on the surface and adjuvant monophosphoryl lipid A (MPLA) encapsulated in the core of poly (D, L-lactide-co-glycolide) (PLGA) nanoparticles. PLGA itself possessed the ability of antigen capture. TMTP1 was a tumor-homing peptide screened by our research team, which held extensive and excellent tumor targeting ability. After these modifications, NP-TP1@M-M could capture and enrich more tumor-specific antigens after chemotherapy, stimulate DC maturation, activate the adaptive immunity and combined with immune checkpoint blockade to maximize the release of the body's immune potential, providing an eutherapeutic strategy for the treatment of OC.

Keywords: Antigen capture; Cancer vaccine; Combination therapy; Nano-vaccine; Ovarian cancer; TMTP1.

MeSH terms

  • Animals
  • Antigens, Neoplasm* / immunology
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • B7-H1 Antigen*
  • Cancer Vaccines* / therapeutic use
  • Cell Line, Tumor
  • Dendritic Cells / drug effects
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / pharmacology
  • Immunotherapy / methods
  • Lipid A / analogs & derivatives
  • Lipid A / chemistry
  • Lipid A / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Nanoparticles* / chemistry
  • Nanovaccines
  • Ovarian Neoplasms* / drug therapy
  • Peptides / chemistry
  • Peptides / pharmacology
  • Polylactic Acid-Polyglycolic Acid Copolymer / chemistry

Substances

  • Cancer Vaccines
  • B7-H1 Antigen
  • Antigens, Neoplasm
  • Peptides
  • Lipid A
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • monophosphoryl lipid A
  • Antineoplastic Agents
  • Immune Checkpoint Inhibitors
  • Nanovaccines