Provided are anti-B7S1 (B7-H4) polypeptides including anti-B7S1 (B7-H4) antibodies and their immunoreactive fragments, chimeric antigen receptor (CAR) binding to B7S1 (B7-H4) molecule and the uses thereof, particularly in the treatment of cancers. The invention particularly concerns humanized anti-B7S1 antibodies and their antigen binding fragments capable of enhancing the activation of the immune system against diseased tissues including cancerous cells, and the genetically engineered immune cells expressing anti-B7S1 CAR used for treatment of diseases including cancers.
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