New emerging targets in cancer immunotherapy: CD27 (TNFRSF7)

Abstract

Cluster of differentiation 27 (CD27) is a member of the tumour necrosis factor receptor superfamily and plays a key role in T-cell activation by providing a costimulatory signal. Bound to its natural ligand CD70, CD27 signalling enhances T-cell proliferation and differentiation to effector and memory T cells and therefore has potential as an immune modulatory target in cancer treatment. The CD27 agonistic antibody varlilumab showed promising efficacy in haematological as well as solid cancers. Current studies investigate the combination of the CD27 agonistic antibody varlilumab in combination with the PD1 axis targeting immune checkpoint inhibitors like nivolumab or atezolizumab. Further, CD70 expression is used as a therapeutic target for ADCs, antibodies inducing ADCC, as well as the immunological target for chimeric antigen receptor gene-modified T cells and specific dendritic cell vaccination. In line with this, targeting the CD27 axis was shown to be feasible and safe in early clinical trials with the most commonly occurring side effects being thrombocytopenia, fatigue and nausea. In this mini review, we aimed to elucidate the immunobiology of CD27 and its potential as a target in cancer immunotherapy.

Checkpoint proteins in patients with precancer and cervical cancer

“…preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in The copyright holder for this this version posted February 9, 2021. ; https://doi.org/10.1101/2021.02.09.430409 doi: bioRxiv preprint established for the development of autoimmune (systemic lupus erythematosus), viral (HIV infection) and some oncological diseases (Hodgkin lymphoma, prostate cancer, lung cancer, breast cancer, colon cancer, glioblastoma, etc.) [34,35,36]. We have not found any literature showing data on the study of sCD27 in CC patients.…”

“…cancer, colon cancer, glioblastoma, etc.) [34,35,36]. We have not found any literature showing data on the study of sCD27 in CC patients.…”

Transcriptome analysis of the procession from chronic pancreatitis to pancreatic cancer and metastatic pancreatic cancer

“…Activation of the CD27/CD70 axis might have immune suppressive effects. CD27 enhanced survival signal in Tregs and induction of apoptosis of effector T cells 33 . And other genes are thought to be closely related to pancreatic cancer, such as LCK 34 .…”

Trial watch: TLR3 agonists in cancer therapy

“…In this trial, vaccination is adjuvanted with Hiltonol™ and montanide ISA-51, 233 as well as with varlilumab. [234][235][236] The status of the following clinical trials discussed in our previous Trial Watches dealing with TLR3 agonists 90 has changed during the past 19 months: NCT02334735, NCT02544880, NCT02721043, NCT02826434, NCT02873819, NCT02897765, NCT03162562, NCT03358719, NCT03380871 and NCT03597282 which are now listed as "Active, not recruiting"; NCT02886065, which is listed as "Recruiting"; NCT02134925 which is currently listed as "Active, not recruiting with results"; NCT02149225, which is listed as "Completed"; NCT03206047 and NCT03300817, which have been "Suspended"; NCT02061449 which has been "Terminated"; as well as NCT02754362, which has been "Withdrawn" (source http:// clinicaltrials.gov/).…”

“…To the best of our knowledge, the results of NCT02149225 (a Phase I study investigating the safety and preliminary efficacy of a Hiltonol™-adjuvanted vaccine in glioblastoma patients) have not been disseminated yet. NCT03206047 (a Phase I/II trial testing Hiltonol™-adjuvanted DC-targeting vaccine in women with recurrent ovarian, fallopian tube, or primary peritoneal cancer) and NCT03300817 (a Phase I study testing a Hiltonol™-adjuvanted, MUC1-targeting vaccine to prevent lung cancer in former and current smokers) have been suspended for undisclosed reasons or to ensure patient safety during the Covid19 epidemics, 237 – 239 respectively (source http://clinicaltrials.gov/ ). NCT02061449 (a Phase I study investigating Hiltonol™ plus radiation in patients with advanced cutaneous T cell lymphoma) has been terminated because of poor accrual.…”