The Cancer Cell and Gene Therapy (CCGT) Program is a component of the overall Center for Cell and Gene Therapy, which is a tri-institutional collaboration among Baylor College of Medicine, Houston Methodist Hospital and Texas Children's Hospital. Under the aegis of these institutions, the center thrives in its mission to conduct basic and translational research that will lead to evidence-based clinical treatments and to share our core scientific expertise in cell and gene therapies with other programs.
The CCGT program has 26 research members and 15 clinical members from several departments including Medicine, Pediatrics, Surgery, Immunology, Molecular and Cell Biology, and Human Genetics. Research focuses on biological questions in stem cell biology, hemopoietic stem cell transplantation, and the active and adoptive immunotherapy of malignancy. The CCGT program also runs two hemopoietic stem cell transplant and cell therapy programs, one for children at the Texas Children's Hospital (in collaboration with its Pediatric Cancer Program).Together, these facilities perform approximately 300 transplants per year and administer over 140 immune-effector cell infusions (over 60 of which are commercial products and over 100 via investigator-initiated studies).
The purpose of the CCGT program to conduct basic research that informs clinical translational studies and to transition between the two rapidly, but safely. We are facilitated in this aim by our Lymphoma Specialized Program of Research Excellence (SPORE), our National Heart, Lung, and Blood Institute (NHLBI) program grant on graft versus host disease (GCHD), and our National Cancer Institute (NCI) program grant on clonal hematopoiesis.
The program is organized in three major research themes each with a basic and clinical/translational leader:
- Normal and Malignant Stem Cell Biology
- Adoptive Cellular Immunotherapy of Cancer
- Improving the Outcome of Hemopoietic Stem Cell Transplantation
Normal and Malignant Stem Cell Biology
Basic Leader: Benjamin Deneen, Ph.D.
Clinical/Translational Leader: Katherine King, M.D., Ph.D.
Research from this theme explores the causes of malignant tumors by looking into the mechanisms of embryonic stem cell biology (cell development) and interactivity of multiple tissue-specific stem cells during the formation of complex organs (cell differentiation). The similarities between these processes in both normal and malignant stem or progenitor cells is becoming increasingly evident, as is the contribution to tumor growth by normal cellular elements that develop from normal progenitor cells in the tumor bed. Hence, all investigators described uunder this theme have made efforts to ensure that the cancer-oriented aspects of their work are appropriately acknowledged and explored. Two principal areas of focus are clonal hemopoiesis and cancer neuroscience.
Selected Recent Publications
Huang-Hobbs E, Cheng YT, Ko Y, Luna-Figueroa E, Lozzi B, Taylor KR, McDonald M, He P, Chen HC, Yang Y, Maleki E, Lee ZF, Murali S, Williamson MR, Choi D, Curry R, Bayley J, Woo J, Jalali A (TB), Monje M, Noebels JL, Harmanci AS, Rao G (CCGT), Deneen B (CCGT). Remote neuronal activity drivecs glioma progression through SEMA4F. Nature. 2023 JUN 28;. DOI: 10.1038/s41586-023-06267-2. Jun 28. PubMed PMID: 37380778; PMCID:7367763
Curry RN, Aiba I, Meyer J (CCGT), Lozzi B, Ko Y, McDonald MF, Rosenbaum A, Cervantes A, Huang-Hobbs E, Cocito C, Greenfield JP, Jalali A (TB), Gavvala J, Mohila C, Serin Harmanci A, Noebels J, Rao G (CCGT), Deneen B (CCGT). Glioma epileptiform activity and progression are driven by IGSF3-mediated potassium dysregulation. Neuron. 2023 MAR 01; 111 (5): 682-695.e9. DOI: 10.1016/j.neuron.2023.01.013. 2023 Feb 13. PubMed PMID: 36787748; PMCID: PMC9991983
Ramabadran R, Wang JH, Reyes JM, Guzman AG, Gupta S, Rosas C, Brunetti L, Gundry MC, Tovy A, Long H, Gu T, Cullen SM, Tyagi S, Rux D, Kim JJ, Kornblau SM, Kyba M, Stossi F, Rau RE (PCP), Takahashi K, Westbrook TF (BCP), Goodell MA (CCGT). DNMT3A-coordinated splicing governs the stem state switch towards differentiation in embryonic and haematopoietic stem cells. Nat Cell Biol. 2023 APR 01; 25(4):528-539. DOI: 10.1038/s41556-023-01109-9. 2023 Apr 6. PubMed PMID: 37024683; PMCID: 2935898
Hormaechea-Agulla D, Matatall KA, Le DT, Kain B, Long X, Kus P, Jaksik R, Challen GA, Kimmel M, King KY (CCGT). Chronic infection drives Dnmt3a-loss-of-function.clonal hematopoiesis via IFNγ signaling. Cell Stem Cell. 2021.03.002. 2021 MAR 19. PubMed PMID: 33743191; PMCID: PMC8349829.
Adoptive Cellular Immunotherapy of Cancer
Basic Leader: Cliona Rooney, Ph.D.
Clinical/Translational Leader: Carlos Ramos M.D.
Basic and translational researchers in this theme are identifying new targets for immunotherapy in various cancers, using tumor antigens to prompt the body's own immune response and developing strategies that overcome tumor evasion mechanisms to immunotherapy. Our translational investigators are moving cell and gene-based therapies from the bench to the bedside in a series of small-scale, iterative laboratory-clinical laboratory protocols, and are also developing pivotal later phase clinical trials. Major accomplishments include mapping the activity of virus-specific cytotoxic T lymphocytes (immune cells) in virus-associated cancers and studies showing the anti-tumor activity of genetically modified T cells in subjects with neuroblastoma, lymphoma, leukemia, and liver cancer.
Selected Recent Publications
Ramos CA, (CCGT), Grover NS, Beaven AW, Lulla PD (CCGT), Wu MF, Ivanova A, Wang T (CCGT), Shea TC, Rooney CM (CCGT), Dittus C, Park SI, Gee AP (CCGT), Eldridge PW, McKay KL, Mehta B, Cheng CJ, Buchanan FB, Grillen BJ (CCGT), Morrison K, Brenner MK (CCGT), Serody JS, Dotti G, Heslop HE (CCGT), Salvado B. Anti-CD30 CAR-T Cell Therapy in Relapsed and Refractory Hodgkin Lymphoma. J Clin Oncol. 2020 NOV 10; 38(32):3794-3804. DOI: 10.1200/JCO.20.01342. 2020 Jul 23. PubMed PMID: 32701411; PMCID: PMC7655020
Mo F, Watanabe N (CCGGT), McKenna MK (CCGT), Hicks MJ (PCP), Srinivasan M, Gomes-Silva D, Atilla E, Smith T, Ataca Atilla P, Ma R, Quach D, Heslop HE (CCGT), Brenner MK (CCGT), Mamonkin M (CCGT). Engineered off-the-shelf therapeutic T cells resist host immune rejection. Nat Biotechnol. 2021 JAN 01; 39(1):56-63. DOI: 10.1038/s41587-020-0601-5. 2020 Jul 13. PubMed PMID:32661440; PMCID: PMC7854790
Steffin D (CCGT), Muhsen IN, Hill LC (CCGT), Ramos CA (CCGT), Ahmed N (PCP), Hegde M (PCP), Wang T (CCGT), Wu M (NA), Gottschalk S, Whittle SB (PCP), Lulla P (CCGT), Mamonkin M (CCGT), Omer B (CCGT), Rouge RH (CCGT), Heczey AA (PCP), Metelitsa LS (PCP), Grillen B (CCGT), Robertson C, Torrano V, Lapteva N (CCGT), Gee AP (CCGT), Rooney C (CCGT), Brenner MK (CCGT), Heslop HE (CCGT). Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IEC's. Blood. 2022 JUL 07; 140(1): 16-24. DOI: 10.1182/blood.2022015728. PubMed PMID:35325065.
Wang D (CCGT), Porter CE, Lim B (BCP), Rosewell Shaw A (CCGT), Robertson CS, Woods ML, Xu Y, Biegert GGW, Morita D, Wang T (CCGT), Grilley BJ (CCGT), Heslop H (CCGT), Brenner MK (CCGT), Suzuki M (CCGT). Ultra-low dose binary oncolytic/helper-dependent adenovirus promotes antitumor activity in preclinical and clinical studies. Sci Adv. 2023 MAR 29; 9(13):eade6790. DOI: 10.1126/sciadv.ade6790. 2023 Mar 29. PubMed PMID: 36989357; PMCID: PMC10058234.
Improving the Outcome of Stem Cell Transplantation for Cancer
Basic Leader: Malcolm Brenner, M.D. Ph.D
Clinical/Translational Leader: LaQuisa Hill, M.D.
Clinical researchers from this group run the adult and pediatric (in collaboration with Texas Children's Hospital's Pediatric Oncology Program) hemopoietic stem cell (HSC) transplant programs. Their research involves applying new modes of HSC transplantation for various malignancies promote durable patient responses to treatment. For example, post-transplant immunotherapy to augmenting graft-versus-tumor activity, reonstituting anti-viral immunity, and strategies to control GVHD while preserving the graft-versus-leukemia effect are just a few approaches being explored. This research has generated robust preclinical data from which several NCI-funded clinical trials have emerged.
Selected Recent Publications
Mo F, Watanabe N (CCGT), Omdahl KI, Burkhardt PM, Ding X, Hayase E, Panoskaltsis-Mortari A, Jena RR, Heslop HE (CCGT), Kean LS, Brenner MK (CCGT), Tkachev V, Mamonkin M (CCGT). Engineering T cells to suppress acute GVHD and leukemia relapse after allogeneic hematopoietic stem cell transplantation. Blood. 2023 MAR 09; 141(10): 1194-1208. DOI: 10.1182/blood.2022016052. PubMed PMID: 36044667; PMCID: PMC10023730.
Pfeiffer T, Tzannou I, Wu M (NA), ), Ramos C (CCGT), Sasa G, Martinez C (CCGT), Lulla P (CCGT), Krance RA (PCP), Scherer L, Ruderfer D, Maik S, Bocchini C, Fraser IP, Patel B, Ward D, Wang T (CCGT), Heslop HE (CCGT), Leen AM (CCGT), Omer B (CCGT). Posoleucel, an Allogeneic, Off-the-Shelf Multivirus-Specific T-Cell Therapy, for the Treatment of Refractory Viral Infections in the Post-HCT Setting. Clin Cancer Res. 2023 JAN 17; 29(2):324-330. DOI:10.1158/1078-0432. CCR-22-2415. PubMed PMID: 36628536; PMCID: PMC9843433.
Naik S, Vasileiou S, Tzannou I, Kuvalekar M, Watanabe A, Robertson C, Lapteva N (CCGT), Tao W, Wu M (NA), Grilley B (CCGT), Carom G (CCGT), Kamble RT (CCGT), Hill LC (CCGT), Krance RA (PCP), Martinez C (CCGT), Tewari P, Omer B (CCGT), Gottschalk S, Heslop HE (CCGT), Brenner MK (CCGT), Rooney C (CCGT), Vera JF, Leen AM (CCGT), Lulla P (CCGT). Donor-derived multiple leukemia antigen-specific T-cell therapy to prevent relapse after transplant in patients with ALL. Blood. 2022 APR 28; 139(17): 2706-2711. DOI: 10.1182/blood.2021014648. PubMed PMID: 35134127; PMCID PMC 9053698.
Seike K, Kiledal A, Fujiwara H, Henig I, Burgos da Silva M, van den Brink MRM, Hein R, Hoostal M, Liu C, Oravecz-Wilson K, Lauder E, Li L, Sun Y, Schmidt TM, Shah YM, Jenq RR, Dick G, Reddy P. Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation. Immunity. 2023; 56(2): 353-68 e6. Pub 20230202.
These activities are supported by two manufacturing laboratories which prepare gene transfer vectors and purified and modified cells made to meet current Good Manufacturing or Good Tissue Practice guidelines. The cell therapy laboratory is a CPRIT supported core facility.
For more information, visit the Center for Cell and Gene Therapy web site.