Recently, researchers have explored several strategies such as intratumoral (IT) administration, design of 4-1BB bispecific antibodies targeting tumor antigens or tumor matrix components, development of proteolytic activation antibodies, and design of tumor-targeting 4-1BB novel antibodies without Fc segments; these are expected to eliminate the key factors causing toxicity while improving the accuracy of antibodies attacking tumors, so that 4-1BB agonists achieve the goal of high efficiency and low toxicity (55, 56). This evidence concerns the gene TNFRSF9 and neoplasm.