The Role of CD30 in Cancer Immunotherapy

Cancer immunotherapy is an exciting field that has revolutionized cancer treatment, with the potential to cure even advanced cancers. Therapies that target immune checkpoints such as PD-1/PD-L1 and CTLA-4 have shown remarkable efficacy in treating many cancer types. However, they are not effective in all patients, and some tumors exhibit resistance to these therapies. Therefore, there is a need to explore alternative mechanisms that can augment or complement the current therapies. In this post, we will discuss the role of CD30 in cancer immunotherapy and its potential as a therapeutic target.

TNF is a cytokine that plays a crucial role in homeostasis and inflammation. It is produced by various cells, including immune cells and tumor cells, and can act either as a pro-inflammatory or an anti-inflammatory agent. TNF receptors are expressed in many cell types, including immune cells, and their interaction with TNF can modulate various immune responses, including cell proliferation, differentiation, and death. CD30 is a TNF receptor that is expressed mainly on activated T cells and some B cells and can modulate T cell activation, survival, and cytokine secretion. CD30 is also expressed in some tumor cells, making it a potential target for cancer immunotherapy.

Studies have shown that CD30 can play a significant role in certain types of lymphomas, such as Hodgkin's and anaplastic large cell lymphomas. CD30-targeted therapies, such as the antibody-drug conjugate Brentuximab Vedotin, have shown significant efficacy in treating these lymphomas. However, their efficacy in other tumor types and in combination with other immunotherapies remains unclear. Additionally, CD30 expression in non-lymphoid tumors is often low, limiting its potential as a universal target for cancer immunotherapy.

Recent studies have suggested that CD30-targeted therapies can enhance the efficacy of PD-1/PD-L1 checkpoint inhibitors. This is because CD30 activation can increase the infiltration and activation of T cells in tumors, leading to increased tumor cell killing. CD30-targeted therapies can also enhance the expression of other immune checkpoint molecules such as ICOS and OX40, further augmenting the anti-tumor immune response. Combination therapies using PD-1/PD-L1 inhibitors and CD30-targeted therapies are currently being explored in clinical trials and early results are promising.

Another potential use of CD30-targeted therapies is in CAR-T cell therapy. CAR-T cells are T cells that have been genetically engineered to express a chimeric antigen receptor (CAR) that recognizes and binds to specific tumor antigens, leading to tumor cell killing. However, CAR-T cell therapy has limitations, such as antigen escape and CAR-T cell exhaustion. CD30-targeted therapies can enhance CAR-T cell activity by activating T cell survival and proliferation pathways, leading to improved tumor cell killing and prolonged efficacy. In preclinical studies, CD30-targeted CAR-T cells have shown efficacy in treating lymphoma and solid tumors.

CD30 is a promising target for cancer immunotherapy, particularly in combination with other immunotherapies such as PD-1/PD-L1 inhibitors and CAR-T cell therapy. However, its potential use is limited by its variable expression in different tumor types and its role in non-tumor diseases. More studies are needed to fully understand the role of CD30 in the immune system and its potential as a therapeutic target. Nonetheless, CD30-targeted therapies hold great promise in improving the efficacy and scope of cancer immunotherapy.

References

van der Weyden, C., Pileri, S., Feldman, A. et al. Understanding CD30 biology and therapeutic targeting: a historical perspective providing insight into future directions. Blood Cancer J. 7, e603 (2017). https://doi.org/10.1038/bcj.2017.85