Immunogenetic Association of 127 Human Leukocyte Antigen (HLA) Alleles with 30 Cancers in Continental Western European Countries
Human leukocyte antigen (HLA) genes have been associated with susceptibility and protection against a number of cancers. Here we used an immunogenetic epidemiological approach to evaluate the overall influence of 127 HLA Class I and II alleles on 30 types of cancer. We found a preponderance of protective alleles (negatively correlated with cancer prevalences), especially for HLA Class I. Of the 30 cancers investigated, 13 were associated with mostly protective HLA effects whereas only 2 were associated with mostly susceptibility HLA alleles. Taken together, these findings highlight the broad influence of HLA on cancer and the complexity of HLA-cancer associations.
DOI: 10.29245/2578-3009/2022/2.1227 View / Download PdfBispecific Antibodies as an Alternative to Antibody Cocktails for SARS-CoV-2: A Mini- Review
Vaccination is a powerful inducer of immunity against SARS-CoV-2 and its recent variants. However, it is important to expand the defensive repertoire against this virus as vaccination is not always efficacious or accessible to everyone. Protein therapeutics in the form of monoclonal antibodies have been used to neutralize the Spike protein, but their efficacy has been limited with rapidly evolving mutations. Cocktail antibodies have been used to combat antigenic escape through diversifying antigen recognition and the overall neutralization capacity. However, the production of cocktail antibodies can be costly and requires a high dosage to achieve the desired therapeutic effect. Alternatively, bispecific antibodies have been used, which contain two recognition specificities within the same molecule. This effectively reduces the cost of production and dosage required to achieve a target therapeutic effect. Bispecific antibodies were reported to bind SARS-CoV-2 antigen with nanomolar affinities. The neutralization potentials (IC50 values) within the same studies were generally more efficacious than their cocktail antibody counterparts. Some studies showed that bispecific antibodies could also confer additional neutralization effector functions, such as recruiting the complement system. Although the recognition of variants was diverse, to our knowledge, there is no data to suggest that bispecific antibodies have a broader recognition of variant strains than cocktail antibodies. Future studies should aim to explore the clinical benefits of bispecific antibodies for SARS-CoV-2 and the emerging variant strains to better understand its benefits in treatment.
DOI: 10.29245/2578-3009/2022/2.1237 View / Download PdfProtective and Susceptibility Effects of Human Leukocyte Antigen on Melanoma Prevalence and their Implications for Predicting Checkpoint Blockade Immunotherapy Outcomes
The association of Human Leukocyte Antigen (HLA) with melanoma has been well documented. Similarly, the outcome of checkpoint blockade immunotherapy (CBI) in melanoma depends, to some extent, on the HLA genotype of the patient. Although specific favorable (or unfavorable) HLA alleles for CBI outcome for melanoma have been identified, there is currently no reliable way to predict a positive, neutral or negative melanoma CBI outcome for other alleles. Here we used an immunogenetic epidemiological approach to identify HLA alleles whose frequency is negatively (or positively) associated with melanoma prevalence (protective or susceptibility alleles, respectively). The findings demonstrated that, indeed, HLA alleles that are negatively associated with melanoma prevalence in the population have been associated with good CBI outcome at the individual level and, conversely, HLA alleles that are positively associated with melanoma prevalence have been associated with poor CBI outcome in individuals. Given this good prediction of CBI cancer immunotherapy by specific immunogenetically discovered HLA alleles, we used this epidemiologic immunogenetic approach to identify more HLA Class I and II alleles protective (or susceptibility) for melanoma which would thus be good predictors of CBI outcomes in those cancers. This is a new approach to successfully (a) identify HLA protective or susceptibility alleles for melanoma, and (b) use that information in anticipating outcomes in CBI cancer immunotherapy.
DOI: 10.29245/2578-3009/2022/2.1238 View / Download Pdf