Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma.

Animals Apoptosis B-Cell Maturation Antigen / genetics CD8-Positive T-Lymphocytes / immunology Cell Proliferation Drug Evaluation, Preclinical Humans Immunotherapy, Adoptive / methods Male Mice Mice, Inbred NOD Mice, SCID Multiple Myeloma / immunology RNA, Messenger / genetics Receptors, Chimeric Antigen / immunology Tumor Cells, Cultured Xenograft Model Antitumor Assays

Journal

Leukemia
ISSN: 1476-5551
Titre abrégé: Leukemia
Pays: England
ID NLM: 8704895

Informations de publication

Date de publication:
03 2021
Historique:
received: 10 05 2020
accepted: 24 06 2020
revised: 18 06 2020
pubmed: 8 7 2020
medline: 23 3 2021
entrez: 8 7 2020
Statut: ppublish

Résumé

Chimeric antigen receptor (CAR) T-cell therapy remains limited to select centers that can carefully monitor adverse events. To broaden use of CAR T cells in community clinics and in a frontline setting, we developed a novel CD8+ CAR T-cell product, Descartes-08, with predictable pharmacokinetics for treatment of multiple myeloma. Descartes-08 is engineered by mRNA transfection to express anti-BCMA CAR for a defined length of time. Descartes-08 expresses anti-BCMA CAR for 1 week, limiting risk of uncontrolled proliferation; produce inflammatory cytokines in response to myeloma target cells; and are highly cytolytic against myeloma cells regardless of the presence of myeloma-protecting bone marrow stromal cells, exogenous a proliferation-inducing ligand, or drug resistance including IMiDs. The magnitude of cytolysis correlates with anti-BCMA CAR expression duration, indicating a temporal limit in activity. In the mouse model of aggressive disseminated human myeloma, Descartes-08 induces BCMA CAR-specific myeloma growth inhibition and significantly prolongs host survival (p < 0.0001). These preclinical data, coupled with an ongoing clinical trial of Descartes-08 in relapsed/refractory myeloma (NCT03448978) showing preliminary durable responses and a favorable therapeutic index, have provided the framework for a recently initiated trial of an optimized/humanized version of Descartes-08 (i.e., Descartes-11) in newly diagnosed myeloma patients with residual disease after induction therapy.

Identifiants

DOI: 10.1038/s41375-020-0951-5 PMID: 32632095 PMC: PMC7785573
pubmed: 32632095
doi: 10.1038/s41375-020-0951-5
pii: 10.1038/s41375-020-0951-5
pmc: PMC7785573
mid: NIHMS1606632
doi:

Substances chimiques

B-Cell Maturation Antigen 0
RNA, Messenger 0
Receptors, Chimeric Antigen 0
TNFRSF17 protein, human 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

752-763

Subventions

Organisme : NCI NIH HHS
ID : P01 CA155258
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA050947
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA207237
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA100707
Pays : United States

Références

Bolli N, Avet-Loiseau H, Wedge DC, Van Loo P, Alexandrov LB, Martincorena I, et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat Commun. 2014;5:2997.
pubmed: 24429703 pmcid: 3905727 doi: 10.1038/ncomms3997
Kumar SK, Anderson KC. Immune therapies in multiple myeloma. Clin Cancer Res. 2016;22:5453–60.
pubmed: 28151713 doi: 10.1158/1078-0432.CCR-16-0868
Manier S, Salem KZ, Park J, Landau DA, Getz G, Ghobrial IM. Genomic complexity of multiple myeloma and its clinical implications. Nat Rev Clin Oncol. 2017;14:100–13.
pubmed: 27531699 doi: 10.1038/nrclinonc.2016.122
Zhang L, Tai YT, Ho M, Xing L, Chauhan D, Gang A, et al. Regulatory B cell-myeloma cell interaction confers immunosuppression and promotes their survival in the bone marrow milieu. Blood Cancer J. 2017;7:e547.
pubmed: 28338671 pmcid: 5380908 doi: 10.1038/bcj.2017.24
Tai YT, Cho SF, Anderson KC. Osteoclast immunosuppressive effects in multiple myeloma: role of programmed cell death ligand 1. Front Immunol. 2018;9:1822.
pubmed: 30147691 pmcid: 6095980 doi: 10.3389/fimmu.2018.01822
Ghobrial IM, Detappe A, Anderson KC, Steensma DP. The bone-marrow niche in MDS and MGUS: implications for AML and MM. Nat Rev Clin Oncol. 2018;15:219–33.
pubmed: 29311715 doi: 10.1038/nrclinonc.2017.197
Maura F, Bolli N, Angelopoulos N, Dawson KJ, Leongamornlert D, Martincorena I, et al. Genomic landscape and chronological reconstruction of driver events in multiple myeloma. Nat Commun. 2019;10:3835.
pubmed: 31444325 pmcid: 6707220 doi: 10.1038/s41467-019-11680-1
Yan Y, Mao X, Liu J, Fan H, Du C, Li Z, et al. The impact of response kinetics for multiple myeloma in the era of novel agents. Blood Adv. 2019;3:2895–904.
pubmed: 31594763 pmcid: 6784522 doi: 10.1182/bloodadvances.2019000432
An G, Yan Y, Xu Y, Mao X, Liu J, Fan H, et al. Monitoring the cytogenetic architecture of minimal residual plasma cells indicates therapy-induced clonal selection in multiple myeloma. Leukemia. 2020;34:578–88.
pubmed: 31591469 doi: 10.1038/s41375-019-0590-x
Chim CS, Kumar SK, Orlowski RZ, Cook G, Richardson PG, Gertz MA, et al. Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond. Leukemia. 2018;32:252–62.
pubmed: 29257139 doi: 10.1038/leu.2017.329
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, et al. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.
pubmed: 23527958 pmcid: 23527958 doi: 10.1056/NEJMoa1215134
Maude SL, Frey N, Shaw PA, Aplenc R, Barrett DM, Bunin NJ, et al. Chimeric antigen receptor T cells for sustained remissions in leukemia. N Engl J Med. 2014;371:1507–17.
pubmed: 25317870 pmcid: 4267531 doi: 10.1056/NEJMoa1407222
Brudno JN, Kochenderfer JN. Chimeric antigen receptor T-cell therapies for lymphoma. Nat Rev Clin Oncol. 2018;15:31–46.
pubmed: 28857075 doi: 10.1038/nrclinonc.2017.128
Park JH, Riviere I, Gonen M, Wang X, Senechal B, Curran KJ, et al. Long-term follow-up of CD19 CAR therapy in acute lymphoblastic leukemia. N Engl J Med. 2018;378:449–59.
pubmed: 6637939 pmcid: 6637939 doi: 10.1056/NEJMoa1709919
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory diffuse large B-cell lymphoma. N Engl J Med. 2019;380:45–56.
doi: 10.1056/NEJMoa1804980
June CH, O’Connor RS, Kawalekar OU, Ghassemi S, Milone MC. CAR T cell immunotherapy for human cancer. Science. 2018;359:1361–65.
pubmed: 29567707 doi: 10.1126/science.aar6711
June CH, Sadelain M. Chimeric antigen receptor therapy. N Engl J Med. 2018;379:64–73.
pubmed: 29972754 pmcid: 7433347 doi: 10.1056/NEJMra1706169
Tai YT, Li XF, Breitkreutz I, Song W, Neri P, Catley L, et al. Role of B-cell-activating factor in adhesion and growth of human multiple myeloma cells in the bone marrow microenvironment. Cancer Res. 2006;66:6675–82.
pubmed: 16818641 doi: 10.1158/0008-5472.CAN-06-0190
Carpenter RO, Evbuomwan MO, Pittaluga S, Rose JJ, Raffeld M, Yang S, et al. B-cell maturation antigen is a promising target for adoptive T-cell therapy of multiple myeloma. Clin Cancer Res. 2013;19:2048–60.
pubmed: 23344265 pmcid: 3630268 doi: 10.1158/1078-0432.CCR-12-2422
Tai YT, Mayes PA, Acharya C, Zhong MY, Cea M, Cagnetta A, et al. Novel anti-B-cell maturation antigen antibody-drug conjugate (GSK2857916) selectively induces killing of multiple myeloma. Blood. 2014;123:3128–38.
pubmed: 24569262 pmcid: 4023420 doi: 10.1182/blood-2013-10-535088
Tai YT, Anderson KC. Targeting B-cell maturation antigen in multiple myeloma. Immunotherapy. 2015;7:1187–99.
pubmed: 26370838 pmcid: 4976846 doi: 10.2217/imt.15.77
Lee L, Bounds D, Paterson J, Herledan G, Sully K, Seestaller-Wehr LM, et al. Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma. Br J Haematol. 2016;174:911–22.
pubmed: 27313079 doi: 10.1111/bjh.14145
Cho SF, Anderson KC, Tai YT. Targeting B cell maturation antigen (BCMA) in multiple myeloma: potential uses of BCMA-based immunotherapy. Front Immunol. 2018;9:1821.
pubmed: 30147690 pmcid: 6095983 doi: 10.3389/fimmu.2018.01821
Tai YT, Anderson KC. B cell maturation antigen (BCMA)-based immunotherapy for multiple myeloma. Expert Opin Biol Ther. 2019;19:1143–56.
pubmed: 31277554 pmcid: 6785394 doi: 10.1080/14712598.2019.1641196
Brudno JN, Maric I, Hartman SD, Rose JJ, Wang M, Lam N, et al. T cells genetically modified to express an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of poor-prognosis relapsed multiple myeloma. J Clin Oncol. 2018;36:2267–80.
pubmed: 29812997 pmcid: 6067798 doi: 10.1200/JCO.2018.77.8084
Cohen AD, Garfall AL, Stadtmauer EA, Melenhorst JJ, Lacey SF, Lancaster E, et al. B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma. J Clin Invest. 2019;129:2210–21.
pubmed: 30896447 pmcid: 6546468 doi: 10.1172/JCI126397
Raje N, Berdeja J, Lin Y, Siegel D, Jagannath S, Madduri D, et al. Anti-BCMA CAR T-cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019;380:1726–37.
pubmed: 31042825 doi: 10.1056/NEJMoa1817226
Cohen AD, Garfall AL, Dogan A, Lacey SF, Martin C, Lendvai N, et al. Serial treatment of relapsed/refractory multiple myeloma with different BCMA-targeting therapies. Blood Adv. 2019;3:2487–90.
pubmed: 31451444 pmcid: 6712532 doi: 10.1182/bloodadvances.2019000466
Barrett DM, Liu X, Jiang S, June CH, Grupp SA, Zhao Y. Regimen-specific effects of RNA-modified chimeric antigen receptor T cells in mice with advanced leukemia. Hum Gene Ther. 2013;24:717–27.
pubmed: 23883116 pmcid: 3746289 doi: 10.1089/hum.2013.075
Tasian SK, Kenderian SS, Shen F, Ruella M, Shestova O, Kozlowski M, et al. Optimized depletion of chimeric antigen receptor T cells in murine xenograft models of human acute myeloid leukemia. Blood. 2017;129:2395–407.
pubmed: 28246194 pmcid: 5409446 doi: 10.1182/blood-2016-08-736041
Rozemuller H, van der Spek E, Bogers-Boer LH, Zwart MC, Verweij V, Emmelot M, et al. A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect. Haematologica. 2008;93:1049–57.
pubmed: 18492693 doi: 10.3324/haematol.12349
Feng X, Zhang L, Acharya C, An G, Wen K, Qiu L, et al. Targeting CD38 suppresses induction and function of T regulatory cells to mitigate immunosuppression in multiple myeloma. Clin Cancer Res. 2017;23:4290–300.
pubmed: 28249894 pmcid: 5540790 doi: 10.1158/1078-0432.CCR-16-3192
Tai YT, Lin L, Xing L, Cho SF, Yu T, Acharya C, et al. APRIL signaling via TACI mediates immunosuppression by T regulatory cells in multiple myeloma: therapeutic implications. Leukemia. 2019;33:426–38.
pubmed: 30135465 doi: 10.1038/s41375-018-0242-6
Tai YT, Horton HM, Kong SY, Pong E, Chen H, Cemerski S, et al. Potent in vitro and in vivo activity of an Fc-engineered humanized anti-HM1.24 antibody against multiple myeloma via augmented effector function. Blood. 2012;119:2074–82.
pubmed: 22246035 pmcid: 3757461 doi: 10.1182/blood-2011-06-364521
Tai YT, Acharya C, An G, Moschetta M, Zhong MY, Feng X, et al. APRIL and BCMA promote human multiple myeloma growth and immunosuppression in the bone marrow microenvironment. Blood. 2016;127:3225–36.
pubmed: 27127303 pmcid: 4920023 doi: 10.1182/blood-2016-01-691162
Xing L, Lin L, Yu T, Li Y, Cho SF, Liu J, et al. A novel BCMA PBD-ADC with ATM/ATR/WEE1 inhibitors or bortezomib induce synergistic lethality in multiple myeloma. Leukemia. 2020. https://doi.org/10.1038/s41375-020-0745-9 . Online ahead of print.
Avanzi MP, Yeku O, Li X, Wijewarnasuriya DP, van Leeuwen DG, Cheung K, et al. Engineered tumor-targeted T cells mediate enhanced anti-tumor efficacy both directly and through activation of the endogenous immune system. Cell Rep. 2018;23:2130–41.
pubmed: 29768210 pmcid: 5986286 doi: 10.1016/j.celrep.2018.04.051
Wang Z, Han W. Biomarkers of cytokine release syndrome and neurotoxicity related to CAR-T cell therapy. Biomark Res. 2018;6:4.
pubmed: 29387417 pmcid: 5778792 doi: 10.1186/s40364-018-0116-0
Hay KA, Hanafi LA, Li D, Gust J, Liles WC, Wurfel MM, et al. Kinetics and biomarkers of severe cytokine release syndrome after CD19 chimeric antigen receptor-modified T-cell therapy. Blood. 2017;130:2295–306.
pubmed: 28924019 pmcid: 5701525 doi: 10.1182/blood-2017-06-793141
An G, Acharya C, Feng X, Wen K, Zhong M, Zhang L, et al. Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication. Blood. 2016;128:1590–603.
pubmed: 27418644 pmcid: 5034739 doi: 10.1182/blood-2016-03-707547
Schmidts A, Ormhoj M, Choi BD, Taylor AO, Bouffard AA, Scarfo I, et al. Rational design of a trimeric APRIL-based CAR-binding domain enables efficient targeting of multiple myeloma. Blood Adv. 2019;3:3248–60.
pubmed: 31698455 pmcid: 6855119 doi: 10.1182/bloodadvances.2019000703
Tai YT, Landesman Y, Acharya C, Calle Y, Zhong MY, Cea M, et al. CRM1 inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications. Leukemia. 2014;28:155–65.
pubmed: 23588715 doi: 10.1038/leu.2013.115
Ren J, Liu X, Fang C, Jiang S, June CH, Zhao Y. Multiplex genome editing to generate universal CAR T cells resistant to PD1 inhibition. Clin Cancer Res. 2017;23:2255–66.
pubmed: 27815355 doi: 10.1158/1078-0432.CCR-16-1300
D’Agostino M, Raje N. Anti-BCMA CAR T-cell therapy in multiple myeloma: can we do better? Leukemia. 2020;34:21–34.
pubmed: 31780814 doi: 10.1038/s41375-019-0669-4
Cho SF, Lin L, Xing L, Li Y, Yu T, Anderson KC, et al. BCMA-targeting therapy: driving a new era of immunotherapy in multiple myeloma. Cancers. 2020;12:1473.
pmcid: 7352710 doi: 10.3390/cancers12061473 pubmed: 7352710
Xu J, Chen LJ, Yang SS, Sun Y, Wu W, Liu YF, et al. Exploratory trial of a biepitopic CAR T-targeting B cell maturation antigen in relapsed/refractory multiple myeloma. Proc Natl Acad Sci USA. 2019;116:9543–51.
pubmed: 30988175 doi: 10.1073/pnas.1819745116
Teachey DT, Lacey SF, Shaw PA, Melenhorst JJ, Maude SL, Frey N, et al. Identification of predictive biomarkers for cytokine release syndrome after chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Cancer Discov. 2016;6:664–79.
pubmed: 27076371 pmcid: 5448406 doi: 10.1158/2159-8290.CD-16-0040
Sadelain M. CD19 CAR T Cells. Cell. 2017;171:1471.
pubmed: 29245005 doi: 10.1016/j.cell.2017.12.002
Foster JB, Barrett DM, Kariko K. The emerging role of in vitro-transcribed mRNA in adoptive T cell immunotherapy. Mol Ther. 2019;27:747–56.
pubmed: 30819612 pmcid: 6453504 doi: 10.1016/j.ymthe.2019.01.018
Wiesinger M, Marz J, Kummer M, Schuler G, Dorrie J, Schuler-Thurner B, et al. Clinical-scale production of CAR-T cells for the treatment of melanoma patients by mRNA transfection of a CSPG4-specific CAR under full GMP compliance. Cancers. 2019;11:1198.
pmcid: 6721485 doi: 10.3390/cancers11081198 pubmed: 6721485
Foster JB, Choudhari N, Perazzelli J, Storm J, Hofmann TJ, Jain P, et al. Purification of mRNA encoding chimeric antigen receptor is critical for generation of a robust T-cell response. Hum Gene Ther. 2019;30:168–78.
pubmed: 30024272 pmcid: 6383579 doi: 10.1089/hum.2018.145

Auteurs

Liang Lin (L)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Shih-Feng Cho (SF)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.

Lijie Xing (L)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Kenneth Wen (K)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Yuyin Li (Y)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
School of Biotechnology, Key Lab of Industrial Fermentation Microbiology of the Ministry of Education, State Key Laboratory of Food Nutrition and Safety, Tianjin University of Science and Technology, Tianjin, 300457, PR China.

Tengteng Yu (T)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Phillip A Hsieh (PA)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Hailin Chen (H)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
ORCID: 0000-0003-1648-0427

Metin Kurtoglu (M)

Cartesian Therapeutics, Gaithersburg, MD, USA.

Yi Zhang (Y)

Cartesian Therapeutics, Gaithersburg, MD, USA.

C Andrew Stewart (C)

Cartesian Therapeutics, Gaithersburg, MD, USA.
ORCID: 0000-0001-7936-447X

Nikhil Munshi (N)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.

Kenneth C Anderson (KC)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Kenneth_anderson@dfci.harvard.edu.

Yu-Tzu Tai (YT)

Jerome Lipper Multiple Myeloma Center, LeBow Institute for Myeloma Therapeutics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. yu-tzu_tai@dfci.harvard.edu.
ORCID: 0000-0001-6199-3569

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female

Evaluation of Low-Value Services Across Major Medicare Advantage Insurers and Traditional Medicare.

Ciara Duggan, Adam L Beckman, Ishani Ganguli et al.
1.00
Humans United States Aged Cross-Sectional Studies Medicare Part C

Effectiveness of Virtual Yoga for Chronic Low Back Pain: A Randomized Clinical Trial.

Hallie Tankha, Devyn Gaskins, Amanda Shallcross et al.
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Mort cellulaire › Mort cellulaire régulée › Apoptose › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs aux cytokines › Récepteurs aux facteurs de nécrose tumorale › Antigène de maturation des cellules B › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › Lymphocytes T CD8+ › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Phénomènes physiologiques › Croissance et développement › Croissance › Processus de croissance cellulaire › Prolifération cellulaire › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Techniques d'investigation › Évaluation préclinique de médicament › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Techniques d'investigation › Techniques immunologiques › Immunisation passive › Transfert adoptif › Immunothérapie adoptive › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée NOD › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souches mutantes de souris › Souris SCID › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Maladies du système immunitaire › Syndromes immunoprolifératifs › Paraprotéinémies › Myélome multiple › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › ARN messager › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Récepteurs cytoplasmiques et nucléaires › Récepteurs chimériques pour l'antigène › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Preclinical evaluation of CD8+ anti-BCMA mRNA...
questionsmedicales.fr › Techniques d'investigation › Transplantation tumorale › Tests d'activité antitumorale sur modèle de xénogreffe › Preclinical evaluation of CD8+ anti-BCMA mRNA...