Provided herein are novel anti-CD28×anti-MSLN antibodies and methods of using such antibodies for the treatment of MSLN-associated cancers. Subject anti-CD28×anti-MSLN antibodies are capable of agonistically binding to CD28 costimulatory molecules on T cells and MSLN on tumor cells. Thus, such antibodies selectively enhance anti-tumor activity at tumor sites while minimizing peripheral toxicity. The subject antibodies provided herein are particularly useful in combination with other anti-cancer therapies, including, for example, bispecific antibodies for the treatment of MSLN-associated cancers (e.g., ovarian cancers).