The present disclosure provides immunotherapeutic compositions and methods for enhancing an immune response and for treating cancer or inflammatory conditions mediated by autoreactive B cells in a subject. In some aspects, multispecific antigen-binding constructs are provided that recognize at least one tumor antigen or B-lineage cell antigen and NKp30 and/or another activating NK receptor. In some aspects, multispecific antigen-binding constructs are provided that recognize at least two tumor antigens or two antigens expressed by B-lineage cells, NKp30, and another activating NK receptor. The multispecific antigen-binding constructs and methods disclosed herein can be used for the treatment of cancer, even a cancer characterized by a CD16 deficient microenvironment and/or characterized by target cells (e.g., cancer cells) having a low level of expression of the tumor antigen.本發明提供用於增強個體中之免疫反應及用於治療癌症或藉由自體反應性B細胞介導之發炎病狀之免疫治療組合物及方法。在一些態樣中,提供識別至少一種腫瘤抗原或B譜系細胞抗原及NKp30及/或另一活化NK受體之多特異性抗原結合構築體。在一些態樣中,提供識別至少兩種腫瘤抗原或由B譜系細胞表現之兩種抗原、NKp30及另一活化NK受體之多特異性抗原結合構築體。本文所揭示之多特異性抗原結合構築體及方法可用於治療癌症,甚至特徵在於CD16缺乏微環境及/或特徵在於具有該腫瘤抗原之低水準表現之標靶細胞(例如,癌細胞)的癌症。