Clinical progress in the field of HER2-positive breast cancer therapy has been dramatically improved by understanding of the immune regulatory mechanisms of tumor microenvironment. Passive immunotherapy utilizing recombinant monoclonal antibodies (mAbs), particularly trastuzumab and pertuzumab has proved to be an effective strategy in HER2-positive breast cancer treatment. However, resistance to mAb therapy and relapse of disease are still considered important challenges in clinical practice. There are increasing reports on the induction of cellular and humoral immune responses in HER2-positive breast cancer patients. More recently, increasing efforts are focused on using HER2-derived peptide vaccines for active immunotherapy. Here, we discuss the development of various HER2-derived vaccines tested in animal models and human clinical trials. Different formulations and strategies to improve immunogenicity of the antigens in animal studies are also discussed. Furthermore, other immunotherapeutic approaches to HER2 breast cancer including, CTLA-4 inhibitors, immune checkpoint inhibitors, anti PD-1/PD-L1 antibodies are presented.

/pdf/her2-positive-breast-cancer-immunotherapy-a-focus-on-vaccine-58xqxhnoom.pdf

HER2-Positive Breast Cancer Immunotherapy: A Focus on Vaccine Development

Polyactin A is a novel and potent immunological adjuvant for peptide-based cancer vaccine.

Pseudomonas plecoglossicida is the causative agent of visceral granulomas disease (VGD) in large yellow croaker (LYC, Larimichthys crocea) farming. However, multi-antibiotic resistant of P. plecoglossicida creates an urgent need of an efficient vaccine to combat this pathogen. In this study, an inactivated vaccine added polyactin (PA), CpG-riched plasmid (pCpG) and aluminum adjuvant (Al) was developed. As a result, its relative percentage survival (RPS) against P. plecoglossicida were up to 64%. Comparatively, RPS of groups that vaccinated with vaccines adjuvanted with PA and Al or CpG and Al were 49% and 39%. However, an interesting result that the vaccine combined with PA, CpG and Al did not show the strongest activation of total serum protein and antibody levels in serum among three vaccinated groups. According to expressions of some cellular immune related genes, we found that the inactivated vaccine combined with PA, CpG and Al was more likely to induce a cellular immune response rather than humoral immune response. Totally, our study demonstrated that the mixture of PA, CpG and aluminum adjuvant is a potential adjuvant system for LYC vaccine development. 

Polyactin A and CpG enhance inactivated Pseudomonas plecoglossicida vaccine potency in large yellow croaker (Larimichthys crocea)

Polyactin A and CpG enhance inactivated Pseudomonas plecoglossicida vaccine potency in large yellow croaker (Larimichthys crocea).

It discloses a method of coating the particles. The method of at least hydroxyl groups the surface of the particles, the particles (i) containing suitable functional groups for experiencing coupling reaction with a halogen or alkoxy group, the formula (Ia) and / or (Ib) comprising contacting molecule (ii); a is a metal or metalloid, G Molecules of the compound of general formula (Ia) and / or (Ib) by a coupling reaction between the functional group and moiety R Furthermore, the molecules of the compound of general formula (Ia) and / or (Ib) to form a preliminary coating on the particles by crosslinking. The molecule of formula (IIa) and / or (IIb) is added; M is a metal or R G K is a functional group suitable for forming a covalent bond with a functional group E. The formed mixture is exposed to ultrasonic. Whereby covalent bonds between functional groups E and K are formed, molecules of formula (IIa) and / or (IIb) is cross-linked. Thus the coating is formed on the particle.

Method for coating the particles

Preparation and anti-tumor evaluation of polyactin A microparticles from supercritical CO2 processing

This paper reports the use of a coating process based on supercritical fluid technology to prepare a solvent-free microparticles, loaded with a polymannopeptide (polyactin, PAA) for enhanceing optimal host response in cancer immunotherapy.Microparticles were characterized as regards their morphology, drug content and in vitro release . A prolonged release of the PAA had been achieved over a 24 h period from microparticles coated with the lipidic compound, which produced a more homogeneous, film-forming coating. Furthermore, it was shown that PAA did not undergo any degradation under the supercritical conditions used in the coating process. In vitro immunoactivity and anti-tumor effect analysis results showed that the PAA microsphere could efficiently trigger the induction of cytotoxic T lymphocytes (CTL) in a sustained manner.

Preparation and Evaluation of Polyactin Microparticles from Supercritical CO2 Processing

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Preparation and anti-tumor evaluation of polyactin A microparticles from supercritical CO2 processing

Preparation and Evaluation of Polyactin Microparticles from Supercritical CO2 Processing