| Title | Neoadjuvant botensilimab plus balstilimab response pattern in locally advanced mismatch repair proficient colorectal cancer. |
| Publication Type | Journal Article |
| Year of Publication | 2023 |
| Authors | Kasi PMurtaza, Hidalgo M, Jafari MD, Yeo H, Lowenfeld L, Khan U, Nguyen ATH, Siolas D, Swed B, Hyun J, Khan S, Wood M, Samstein B, Rocca JP, Ocean AJ, Popa EC, Hunt DH, Uppal NP, Garrett KA, Pigazzi A, Zhou XKathy, Shah MA, Hissong E |
| Journal | Oncogene |
| Volume | 42 |
| Issue | 44 |
| Pagination | 3252-3259 |
| Date Published | 2023 Oct |
| ISSN | 1476-5594 |
| Keywords | Antibodies, Monoclonal, Humanized, Colorectal Neoplasms, DNA Mismatch Repair, Humans, Neoadjuvant Therapy, Rectal Neoplasms |
| Abstract | In patients with locally advanced cancer without distant metastases, the neoadjuvant setting presents a platform to evaluate new drugs. For mismatch repair proficient/microsatellite stable (pMMR/MSS) colon and rectal cancer, immunotherapy has shown limited efficacy. Herein, we report exceptional responses observed with neoadjuvant botensilimab (BOT), an Fc-enhanced next-generation anti-CTLA-4 antibody, alongside balstilimab (BAL; an anti-PD-1 antibody) in two patients with pMMR/MSS colon and rectal cancer. The histological pattern of rapid immune response observed ("inside-out" (serosa-to-mucosa) tumor regression) has not been described previously in this setting. Spatial biology analyses (RareCyte Inc.) reveal mechanisms of actions of BOT, a novel innate-adaptive immune activator. These observations have downstream implications for clinical trial designs using neoadjuvant immunotherapy and potentially sparing patients chemotherapy. |
| DOI | 10.1038/s41388-023-02835-y |
| Alternate Journal | Oncogene |
| PubMed ID | 37731056 |
| PubMed Central ID | PMC10611560 |
| Grant List | K08 CA241341 / CA / NCI NIH HHS / United States |