Anti-tumor effects induced by gene vaccines co-expressing truncated human prostate specific membrane antigen gene and mouse 4-1BBL

Objective To investigate the influence of m4-1BBL on anti-tumor effects induced by truncated human prostate specific membrane antigen ( tPSMA ) gene in mice. Methods A eukaryotic expression plasmid encoding tPSMA and m4-1BBL ( pDC316-tPSMA-IRES m4-1BBL) ,pDC316-tPSMA and pDC316 were constructed.

Safety,immunogenicity,and cross-species protection of a plasmid DNA encoding Plasmodium falciparum SERA5 polypeptide,microbial epitopes and chemokine genes in mice and olive baboons

Incorporation of biomolecular epitopes to malarial antigens should be explored in the development of straintranscending malarial vaccines.The present study sought to determine safety,immunogenicity and cross-species efficacy of Plasmodium falciparum serine repeat antigen 5 polypeptide co-expressed with epitopes of BacilleCalmette Guerin（BCG）,tetanus toxoid（TT） and a chemokine gene.Olive baboons and BALB/c mice were randomly assigned into vaccine and control groups.The vaccine group animals were primed and boosted twice with pIRES plasmids encoding the SERA5 ＋ BCG ＋ TT alone,or with either CCL5 or CCL20 and the control group with pIRES plasmid vector backbone.Mice and baboons were challenged with P.berghei ANKA and P.knowlesi H strain parasites,respectively.Safety was determined by observing for injection sites reactogenicities,hematology and clinical chemistry.Parasitaemia and survivorship profiles were used to determine cross-species efficacy,and T cell phenotypes,Th1-,Th2-type,T-regulatory immune responses and antibody responses were assessed to determine vaccine immunogenicity.The pSeBCGTT plasmid DNA vaccines were safe and induced Thl-,Th2-type,and Tregulatory responses vaccinated animals showed enhanced CD4~＋（P〈0.01）,CD 8~＋ T cells（P〈 0.001） activation and IgG anti-SE36 antibodies responses（P〈 0.001） at week 4 and 8 post vaccination compared to the control group.Vaccinated mice had a 31.45-68.69%cumulative parasite load reduction and 60%suppression in baboons（P〈0.05）and enhanced survivorship（P〈 0.001） with no clinical signs of malaria compared to the control group.The results showed that the vaccines were safe,immunogenic and conferred partial cross-species protection.

Immuno-oncology in triple-negative breast cancer

The immune system plays an important role in breast cancer.Triple-negative breast cancer(TNBC)has a higher mutational load compared to other subtypes.In addition,higher levels of tumor-associated antigens suggests that immunotherapies are a promising treatment option especially for TNBC.Our review discusses both the complexity of the immune system and the cancer immune-cell cycle.In fact,a higher level of tumor-infiltrating lymphocytes is associated with an improved prognosis as well as a better response to chemotherapy in TNBC.Important target structures within the cancer immune-cell cycle are the so-called“immune checkpoints”.Immune checkpoint inhibitors(ICPi)block the interaction of certain cell surface proteins that serve as“brakes”of immune reactions.Recent studies have shown ICPi improved survival in early as well as advanced TNBC.However,this has the price of increasing,mainly,immune-mediated toxicity.ICPi strengthen tumor-specific T cell-mediated immunity by“releasing the brake”of the immune system.In combination with chemotherapy,ICPi are already approved for TNBC.As a further step,individualized vaccination strategies against tumor-associated neoantigens represent another promising approach.A liposome-formulated intravenous RNA vaccine encoding different tumor-associated antigens is currently being studied in TNBC and leads to neoantigen-specific immune responses.These novel strategies will improve the prognosis of patients with triple-negative breast cancer.