PMID- 32043778 OWN - NLM STAT- MEDLINE DCOM- 20210618 LR - 20220302 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 25 IP - 2 DP - 2020 Feb TI - A Phase I Study of Alpha-1,3-Galactosyltransferase-Expressing Allogeneic Renal Cell Carcinoma Immunotherapy in Patients with Refractory Metastatic Renal Cell Carcinoma. PG - 121-e213 LID - 10.1634/theoncologist.2019-0599 [doi] AB - LESSONS LEARNED: HyperAcute Renal immunotherapy was well tolerated and demonstrated antitumor activity in patients requiring salvage-line treatment for metastatic renal cell carcinoma (mRCC). HyperAcute Renal immunotherapy was safely administered with concomitant salvage-line treatments for mRCC, and it may be a candidate for inclusion in novel combinations for salvage treatment of mRCC because of its unique mechanism of action. BACKGROUND: HyperAcute Renal (HAR) immunotherapy exploits a naturally occurring barrier to xenotransplantation and zoonotic infections in humans to immunize patients against metastatic renal cell carcinoma (mRCC) cells. HAR consists of two allogeneic renal cancer cell lines genetically modified to express alpha(1,3)Gal, to which humans have an inherent pre-existing immunity. METHODS: Patients with refractory mRCC were eligible for this phase I dose-escalation trial. Concomitant treatment was permitted after the initial 2 months of HAR monotherapy. HAR was injected intradermally weekly for 4 weeks then biweekly for 20 weeks, totaling 14 immunizations. The primary endpoint was safety and determination of a maximum tolerated dose (MTD). RESULTS: Among 18 patients enrolled, two grade 3 adverse events (AEs) were attributed to HAR, lymphopenia and injection site reaction, and no grade 4/5 AEs occurred. The recommended phase II dose (RP2D) was 300 million cells. One patient had a partial response and eight patients had stable disease, for a disease control rate of 50% (9/18). Median overall survival with low-dose HAR was 14.2 months and was 25.3 months with high-dose HAR. CONCLUSION: In pretreated mRCC, HAR immunotherapy was well tolerated and demonstrated antitumor activity. HAR immunotherapy may be a candidate for inclusion in novel combinations for salvage treatment of mRCC. CI - (c) AlphaMed Press; the data published online to support this summary are the property of the authors. FAU - Hahn, Andrew W AU - Hahn AW AD - Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. FAU - Drake, Charles AU - Drake C AD - Divison of Hematology/Oncology, Department of Medicine, New York Presbyterian, Columbia University Medical Center, New York, New York, USA. FAU - Denmeade, Samuel R AU - Denmeade SR AD - Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland, USA. FAU - Zakharia, Yousef AU - Zakharia Y AD - Division of Hematology, Oncology, and Blood and Marrow Transplant, Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa, USA. FAU - Maughan, Benjamin L AU - Maughan BL AD - Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. FAU - Kennedy, Eugene AU - Kennedy E AD - NewLink Genetics Corporation, Ames, Iowa, USA. FAU - Link, Charles Jr AU - Link C Jr AD - NewLink Genetics Corporation, Ames, Iowa, USA. FAU - Vahanian, Nicholas AU - Vahanian N AD - NewLink Genetics Corporation, Ames, Iowa, USA. FAU - Hammers, Hans AU - Hammers H AD - Division of Hematology/Oncology, Department of Internal Medicine, Harold C. Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas, USA. FAU - Agarwal, Neeraj AU - Agarwal N AD - Division of Oncology, Department of Internal Medicine, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah, USA. LA - eng SI - ClinicalTrials.gov/NCT02035358 PT - Clinical Trial, Phase I PT - Journal Article DEP - 20190906 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - EC 2.4.1.- (Galactosyltransferases) SB - IM MH - *Carcinoma, Renal Cell/drug therapy MH - Galactosyltransferases MH - *Hematopoietic Stem Cell Transplantation MH - Humans MH - Immunotherapy MH - *Kidney Neoplasms/drug therapy MH - Treatment Outcome PMC - PMC7011628 EDAT- 2020/02/12 06:00 MHDA- 2021/06/22 06:00 PMCR- 2020/02/01 CRDT- 2020/02/12 06:00 PHST- 2019/07/20 00:00 [received] PHST- 2019/07/31 00:00 [accepted] PHST- 2020/02/12 06:00 [entrez] PHST- 2020/02/12 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/02/01 00:00 [pmc-release] AID - ONCO13082 [pii] AID - 10.1634/theoncologist.2019-0599 [doi] PST - ppublish SO - Oncologist. 2020 Feb;25(2):121-e213. doi: 10.1634/theoncologist.2019-0599. Epub 2019 Sep 6.