In a comparative preclinical study of CD3zeta, CD28-CD3zeta and CD28-OX40-CD3zeta endodomains of GD2-specific CAR, the CD28-OX40-CD3zeta construct optimized the proliferation, survival and cytolytic capacity of transgenic T cells.10 The sustained cytotoxic functions of the CD28-OX40-CD3zeta containing GD2-CAR manifested as significant antitumor effects of GD2-CAR gene-modified human T cells in a murine model of GD2-expressing human melanoma metastases.9 Importantly, melanoma cell killing by these GD2-CAR gene-modified T cells occurred even when GD2 expression was relatively low.9 Here, CD28 is linked to melanoma.