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1.
Molecules ; 24(18)2019 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-31487832

RESUMO

Sex differences in innate and adaptive immune responses are known, and women generally mount a stronger immune response than men. Cancer immunotherapy, represented by immune checkpoint inhibitors (ICIs), has revolutionized the treatment of cancer, and sex differences in cancer immunotherapy are just starting to be revealed. Here, we summarize recent research progress concerning sex differences in cancer immunotherapy efficacy. On their own, ICIs tend to be more effective in male cancer patients compared with female patients, while ICIs combined with chemotherapy tend to be more effective in female patients than male patients. Male tumors are usually more antigenic than female tumors, and this is reflected by their increased number of tumor mutations and cancer germline antigens. The biomarker tumor mutational burden (TMB), which reflects tumor antigenicity, is more effective at predicting immunotherapy response for female lung cancer patients than for male patients. In this review, we propose different therapeutic strategies for the different sexes: For male cancer patients, the immune environment should be enhanced, whereas for female cancer patients, tumor antigenicity should be enhanced.


Assuntos
Biomarcadores Tumorais , Imunoterapia , Neoplasias/imunologia , Neoplasias/terapia , Antígenos de Neoplasias/imunologia , Feminino , Humanos , Imunidade , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Masculino , Fatores Sexuais , Resultado do Tratamento
2.
Nat Commun ; 15(1): 4857, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849365

RESUMO

Reticulocyte-binding protein homologue 5 (RH5), a leading blood-stage Plasmodium falciparum malaria vaccine target, interacts with cysteine-rich protective antigen (CyRPA) and RH5-interacting protein (RIPR) to form an essential heterotrimeric "RCR-complex". We investigate whether RCR-complex vaccination can improve upon RH5 alone. Using monoclonal antibodies (mAbs) we show that parasite growth-inhibitory epitopes on each antigen are surface-exposed on the RCR-complex and that mAb pairs targeting different antigens can function additively or synergistically. However, immunisation of female rats with the RCR-complex fails to outperform RH5 alone due to immuno-dominance of RIPR coupled with inferior potency of anti-RIPR polyclonal IgG. We identify that all growth-inhibitory antibody epitopes of RIPR cluster within the C-terminal EGF-like domains and that a fusion of these domains to CyRPA, called "R78C", combined with RH5, improves the level of in vitro parasite growth inhibition compared to RH5 alone. These preclinical data justify the advancement of the RH5.1 + R78C/Matrix-M™ vaccine candidate to Phase 1 clinical trial.


Assuntos
Anticorpos Monoclonais , Anticorpos Antiprotozoários , Antígenos de Protozoários , Vacinas Antimaláricas , Malária Falciparum , Plasmodium falciparum , Proteínas de Protozoários , Vacinas Antimaláricas/imunologia , Vacinas Antimaláricas/administração & dosagem , Animais , Plasmodium falciparum/imunologia , Proteínas de Protozoários/imunologia , Feminino , Malária Falciparum/prevenção & controle , Malária Falciparum/imunologia , Malária Falciparum/parasitologia , Antígenos de Protozoários/imunologia , Ratos , Anticorpos Antiprotozoários/imunologia , Anticorpos Monoclonais/imunologia , Humanos , Epitopos/imunologia , Proteínas de Transporte/imunologia , Proteínas de Transporte/metabolismo
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