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The tumor acidic microenvironment is a fundamental characteristic of solid tumors which distinguishes the tumor from adjacent normal tissues. This unique tumor microenvironment (TME) feature directly contributes to various aspect of tumor progression including gene expression, immune suppression, drug resistance, invasion and metastasis. Acidic TME poses great challenges for the efficacy of therapeutics; extracellular acidity of cancer cells provides less permissive conditions for optimal target engagement and drug efficacy. In addition targeting the effectors of acid-base balance enriched in hypoxia and acidic regions of the tumor provide valuable tools for normalizing the extracellular acidity and delivery of therapeutics agents to areas of the tumor less malleable to conventional therapies. Thus in the case of therapeutic antibodies, strategies that specifically integrates this TME specific feature in the design could …