Furthermore, in the B16F10 melanoma tumor model, neither an anti-CTLA-4 VHH single-domain nanobody lacking the Fc-portion nor a pegylated VHH controlled tumor growth in combination with GVAX, while a VHH fusion to mIgG2a restored therapeutic efficacy with reduction of intratumoral Tregs [14]. Here, CTLA4 is linked to neoplasm.