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Article ; Online: Rationale for anti-GITR cancer immunotherapy.

Knee, Deborah A / Hewes, Becker / Brogdon, Jennifer L

European journal of cancer (Oxford, England : 1990)

2016 Volume 67, Page(s) 1–10

Abstract: Over the past decade, our understanding of cancer immunotherapy has evolved from assessing peripheral responses in the blood to monitoring changes in the tumour microenvironment. Both preclinical and clinical experience has taught us that modulation of ... ...

Abstract	Over the past decade, our understanding of cancer immunotherapy has evolved from assessing peripheral responses in the blood to monitoring changes in the tumour microenvironment. Both preclinical and clinical experience has taught us that modulation of the tumour microenvironment has significant implications to generating robust antitumour immunity. Clinical benefit has been well documented to correlate with a tumour microenvironment that contains a dense infiltration of CD8
MeSH term(s)	Animals ; Antibodies, Monoclonal/immunology ; Antibodies, Monoclonal/therapeutic use ; CTLA-4 Antigen/antagonists & inhibitors ; Colonic Neoplasms ; Disease Models, Animal ; Drug Therapy, Combination ; Glucocorticoid-Induced TNFR-Related Protein/agonists ; Glucocorticoid-Induced TNFR-Related Protein/immunology ; Humans ; Immunotherapy/methods ; Melanoma, Experimental ; Molecular Targeted Therapy ; Neoplasms/drug therapy ; Neoplasms/immunology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Receptors, Fc/immunology ; T-Lymphocytes, Regulatory/immunology
Chemical Substances	Antibodies, Monoclonal ; CTLA-4 Antigen ; Glucocorticoid-Induced TNFR-Related Protein ; Programmed Cell Death 1 Receptor ; Receptors, Fc
Language	English
Publishing date	2016-11
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	82061-1
ISSN	1879-0852 ; 0277-5379 ; 0959-8049 ; 0964-1947
ISSN (online)	1879-0852
ISSN	0277-5379 ; 0959-8049 ; 0964-1947
DOI	10.1016/j.ejca.2016.06.028
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Zs.A 456: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 583: Show issues

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Article ; Online: Repeated peripheral infusions of anti-EGFRvIII CAR T cells in combination with pembrolizumab show no efficacy in glioblastoma: a phase 1 trial.

Bagley, Stephen J / Binder, Zev A / Lamrani, Lamia / Marinari, Eliana / Desai, Arati S / Nasrallah, MacLean P / Maloney, Eileen / Brem, Steven / Lustig, Robert A / Kurtz, Goldie / Alonso-Basanta, Michelle / Bonté, Pierre-Emmanuel / Goudot, Christel / Richer, Wilfrid / Piaggio, Eliane / Kothari, Shawn / Guyonnet, Lea / Guerin, Coralie L / Waterfall, Joshua J /

Mohan, Suyash / Hwang, Wei-Ting / Tang, Oliver Y / Logun, Meghan / Bhattacharyya, Meghna / Markowitz, Kelly / Delman, Devora / Marshall, Amy / Wherry, E John / Amigorena, Sebastian / Beatty, Gregory L / Brogdon, Jennifer L / Hexner, Elizabeth / Migliorini, Denis / Alanio, Cecile / O'Rourke, Donald M

Nature cancer

2024 Volume 5, Issue 3, Page(s) 517–531

Abstract: We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a ...

Abstract	We previously showed that chimeric antigen receptor (CAR) T-cell therapy targeting epidermal growth factor receptor variant III (EGFRvIII) produces upregulation of programmed death-ligand 1 (PD-L1) in the tumor microenvironment (TME). Here we conducted a phase 1 trial (NCT03726515) of CAR T-EGFRvIII cells administered concomitantly with the anti-PD1 (aPD1) monoclonal antibody pembrolizumab in patients with newly diagnosed, EGFRvIII
MeSH term(s)	Humans ; Glioblastoma/therapy ; ErbB Receptors ; Neoplasm Recurrence, Local/metabolism ; T-Lymphocytes ; Tumor Microenvironment ; Antibodies, Monoclonal, Humanized
Chemical Substances	pembrolizumab (DPT0O3T46P) ; ErbB Receptors (EC 2.7.10.1) ; Antibodies, Monoclonal, Humanized
Language	English
Publishing date	2024-01-12
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article
ISSN	2662-1347
ISSN (online)	2662-1347
DOI	10.1038/s43018-023-00709-6
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Article: Monitoring of tisagenlecleucel transgene DNA using a quantitative polymerase chain reaction assay.

Davis, Lisa / Riccitelli, Nathan / Valencia, Nancy / Ch'en, Irene L / Tangri, Shabnam / Brogdon, Jennifer L / Kalfoglou, Creton / Mueller, Karen Thudium / Pollner, Reinhold

Molecular therapy. Methods & clinical development

2020 Volume 20, Page(s) 535–541

Abstract: Chimeric antigen receptor (CAR)-T cell therapies reprogram T cells to engage and eliminate cancer cells. Patients' T cells are ... ...

Abstract	Chimeric antigen receptor (CAR)-T cell therapies reprogram T cells to engage and eliminate cancer cells. Patients' T cells are transduced
Language	English
Publishing date	2020-12-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	2872938-9
ISSN	2329-0501 ; 2329-0501
ISSN (online)	2329-0501
ISSN	2329-0501
DOI	10.1016/j.omtm.2020.12.002
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Article ; Online: An IMiD-inducible degron provides reversible regulation for chimeric antigen receptor expression and activity.

Carbonneau, Seth / Sharma, Sujata / Peng, Liaomin / Rajan, Vaisakh / Hainzl, Dominik / Henault, Martin / Yang, Chian / Hale, Jacob / Shulok, Janine / Tallarico, John / Porter, Jeff / Brogdon, Jennifer L / Dranoff, Glenn / Bradner, James E / Hild, Marc / Guimaraes, Carla P

Cell chemical biology

2021 Volume 28, Issue 4, Page(s) 583

Language	English
Publishing date	2021-04-16
Publishing country	United States
Document type	Published Erratum
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2021.02.003
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Article ; Online: A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development.

Dickinson, Michael J / Barba, Pere / Jäger, Ulrich / Shah, Nirav N / Blaise, Didier / Briones, Javier / Shune, Leyla / Boissel, Nicolas / Bondanza, Attilio / Mariconti, Luisa / Marchal, Anne-Laure / Quinn, David S / Yang, Jennifer / Price, Andrew / Sohoni, Akash / Treanor, Louise M / Orlando, Elena J / Mataraza, Jennifer / Davis, Jaclyn /

Lu, Darlene / Zhu, Xu / Engels, Boris / Moutouh-de Parseval, Laure / Brogdon, Jennifer L / Moschetta, Michele / Flinn, Ian W

Cancer discovery

2023 Volume 13, Issue 9, Page(s) 1982–1997

Abstract: CAR T-cell product quality and stemness (Tstem) are major determinants of in vivo expansion, efficacy, and clinical response. Prolonged ex vivo culturing is known to deplete Tstem, affecting clinical outcome. YTB323, a novel autologous CD19-directed CAR ... ...

Abstract	CAR T-cell product quality and stemness (Tstem) are major determinants of in vivo expansion, efficacy, and clinical response. Prolonged ex vivo culturing is known to deplete Tstem, affecting clinical outcome. YTB323, a novel autologous CD19-directed CAR T-cell therapy expressing the same validated CAR as tisagenlecleucel, is manufactured using a next-generation platform in <2 days. Here, we report the preclinical development and preliminary clinical data of YTB323 in adults with relapsed/refractory diffuse large B-cell lymphoma (r/r DLBCL; NCT03960840). In preclinical mouse models, YTB323 exhibited enhanced in vivo expansion and antitumor activity at lower doses than traditionally manufactured CAR T cells. Clinically, at doses 25-fold lower than tisagenlecleucel, YTB323 showed (i) promising overall safety [cytokine release syndrome (any grade, 35%; grade ≥3, 6%), neurotoxicity (any grade, 25%; grade ≥3, 6%)]; (ii) overall response rates of 75% and 80% for DL1 and DL2, respectively; (iii) comparable CAR T-cell expansion; and (iv) preservation of T-cell phenotype. Current data support the continued development of YTB323 for r/r DLBCL. Significance: Traditional CAR T-cell manufacturing requires extended ex vivo cell culture, reducing naive and stem cell memory T-cell populations and diminishing antitumor activity. YTB323, which expresses the same validated CAR as tisagenlecleucel, can be manufactured in <2 days while retaining T-cell stemness and enhancing clinical activity at a 25-fold lower dose. See related commentary by Wang, p. 1961. This article is featured in Selected Articles from This Issue, p. 1949.
MeSH term(s)	Mice ; Animals ; Immunotherapy, Adoptive ; Receptors, Chimeric Antigen ; Lymphoma, Non-Hodgkin ; Lymphoma, Large B-Cell, Diffuse ; Cell Culture Techniques ; Antigens, CD19
Chemical Substances	Receptors, Chimeric Antigen ; Antigens, CD19
Language	English
Publishing date	2023-05-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-22-1276
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Article ; Online: Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells.

Haas, Andrew R / Golden, Ryan J / Litzky, Leslie A / Engels, Boris / Zhao, Linlin / Xu, Fangmin / Taraszka, John A / Ramones, Melissa / Granda, Brian / Chang, Wan-Jung / Jadlowsky, Julie / Shea, Kim-Marie / Runkle, Adam / Chew, Anne / Dowd, Emily / Gonzalez, Vanessa / Chen, Fang / Liu, Xiaojun / Fang, Chongyun /

Jiang, Shuguang / Davis, Megan M / Sheppard, Neil C / Zhao, Yangbing / Fraietta, Joseph A / Lacey, Simon F / Plesa, Gabriela / Melenhorst, J Joseph / Mansfield, Keith / Brogdon, Jennifer L / Young, Regina M / Albelda, Steven M / June, Carl H / Tanyi, Janos L

Molecular therapy : the journal of the American Society of Gene Therapy

2023 Volume 31, Issue 8, Page(s) 2309–2325

Abstract: Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and ... ...

Abstract	Multiple clinical studies have treated mesothelin (MSLN)-positive solid tumors by administering MSLN-directed chimeric antigen receptor (CAR) T cells. Although these products are generally safe, efficacy is limited. Therefore, we generated and characterized a potent, fully human anti-MSLN CAR. In a phase 1 dose-escalation study of patients with solid tumors, we observed two cases of severe pulmonary toxicity following intravenous infusion of this product in the high-dose cohort (1-3 × 10
MeSH term(s)	Humans ; Mesothelin ; GPI-Linked Proteins/genetics ; Immunotherapy, Adoptive/adverse effects ; Immunotherapy, Adoptive/methods ; Neoplasms/therapy ; T-Lymphocytes
Chemical Substances	Mesothelin (J27WDC343N) ; GPI-Linked Proteins
Language	English
Publishing date	2023-06-12
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2010592-7
ISSN	1525-0024 ; 1525-0016
ISSN (online)	1525-0024
ISSN	1525-0016
DOI	10.1016/j.ymthe.2023.06.006
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Article ; Online: OX40 engagement depletes intratumoral Tregs via activating FcγRs, leading to antitumor efficacy.

Bulliard, Yannick / Jolicoeur, Rose / Zhang, Jimin / Dranoff, Glenn / Wilson, Nicholas S / Brogdon, Jennifer L

Immunology and cell biology

2014 Volume 92, Issue 6, Page(s) 475–480

Abstract: Antibodies targeting checkpoint inhibitors or co-stimulatory receptors on T cells have shown significant antitumor efficacy in preclinical and clinical studies. In mouse tumor models, engagement of activating Fcγ receptor (FcγR)-expressing immune cells ... ...

Abstract	Antibodies targeting checkpoint inhibitors or co-stimulatory receptors on T cells have shown significant antitumor efficacy in preclinical and clinical studies. In mouse tumor models, engagement of activating Fcγ receptor (FcγR)-expressing immune cells was recently shown to be required for the tumoricidal activity of antibodies recognizing the tumor necrosis factor superfamily receptor (TNFR) GITR (CD357) and CTLA-4 (CD152). In particular, activating FcγRs facilitated the selective elimination of intratumoral T-cell populations. However, it remains unclear whether FcγRs contribute to the antitumor efficacy of other immunomodulatory antibodies. Here, we explored the mechanism of antitumor activity mediated by an agonistic antibody (clone OX86) to the co-stimulatory TNFR OX40 (CD134). OX40 was highly expressed by intratumoral T cells, particularly those of the FoxP3(+) regulatory T-cell (Treg) lineage. OX86 administration resulted in the depletion of intratumoral regulatory T cells in an activating FcγR-dependent manner, which correlated with tumor regression. Together with previous data from our group and others, these findings support a mechanism whereby antibodies targeting antigens highly expressed by intratumoral T cells can mediate their elimination by FcγR-expressing immune cells, and facilitate subsequent antitumor immunity.
MeSH term(s)	Animals ; CTLA-4 Antigen/genetics ; CTLA-4 Antigen/immunology ; Glucocorticoid-Induced TNFR-Related Protein/genetics ; Glucocorticoid-Induced TNFR-Related Protein/immunology ; Lymphocyte Depletion ; Mice ; Neoplasms, Experimental/genetics ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; Receptors, IgG/genetics ; Receptors, IgG/immunology ; Receptors, OX40/genetics ; Receptors, OX40/immunology ; T-Lymphocytes, Regulatory/immunology ; T-Lymphocytes, Regulatory/pathology
Chemical Substances	CTLA-4 Antigen ; Glucocorticoid-Induced TNFR-Related Protein ; Receptors, IgG ; Receptors, OX40 ; Tnfrsf18 protein, mouse ; Tnfrsf4 protein, mouse
Language	English
Publishing date	2014-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1038/icb.2014.26
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Article ; Online: An IMiD-inducible degron provides reversible regulation for chimeric antigen receptor expression and activity.

Cell chemical biology

2020 Volume 28, Issue 6, Page(s) 802–812.e6

Abstract: The recent development of successful CAR (chimeric antigen receptor) T cell therapies has been accompanied by a need to better control potentially fatal toxicities that can arise from adverse immune reactions. Here we present a ligand-controlled CAR ... ...

Abstract	The recent development of successful CAR (chimeric antigen receptor) T cell therapies has been accompanied by a need to better control potentially fatal toxicities that can arise from adverse immune reactions. Here we present a ligand-controlled CAR system, based on the IKZF3 ZF2 β-hairpin IMiD-inducible degron, which allows for the reversible control of expression levels of type I membrane proteins, including CARs. Testing this system in an established mouse xenotransplantation model for acute lymphoblastic leukemia, we validate the ability of the CAR19-degron to target and kill CD19-positive cells displaying complete control/clearance of the tumor. We also demonstrate that the activity of CAR19-degron can be regulated in vivo when dosing a US Food and Drug Administration-approved drug, lenalidomide.
MeSH term(s)	Adolescent ; Animals ; Cell Line ; Cell Proliferation/drug effects ; Female ; Humans ; Ikaros Transcription Factor/chemistry ; Ikaros Transcription Factor/immunology ; Immunologic Factors/chemistry ; Immunologic Factors/pharmacology ; Male ; Mice ; Mice, Congenic ; Mice, Inbred NOD ; Mice, SCID ; Middle Aged ; Molecular Structure ; Neoplasms, Experimental/drug therapy ; Neoplasms, Experimental/immunology ; Neoplasms, Experimental/pathology ; Receptors, Chimeric Antigen/genetics ; Receptors, Chimeric Antigen/immunology ; T-Lymphocytes/immunology ; Young Adult
Chemical Substances	IKZF3 protein, human ; Immunologic Factors ; Receptors, Chimeric Antigen ; Ikaros Transcription Factor (148971-36-2)
Language	English
Publishing date	2020-12-16
Publishing country	United States
Document type	Journal Article
ISSN	2451-9448
ISSN (online)	2451-9448
DOI	10.1016/j.chembiol.2020.11.012
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Article ; Online: Anti-CD19 CAR T cells in combination with ibrutinib for the treatment of chronic lymphocytic leukemia.

Gill, Saar / Vides, Vanessa / Frey, Noelle V / Hexner, Elizabeth O / Metzger, Susan / O'Brien, Megan / Hwang, Wei-Ting / Brogdon, Jennifer L / Davis, Megan M / Fraietta, Joseph A / Gaymon, Avery L / Gladney, Whitney L / Lacey, Simon F / Lamontagne, Anne / Mato, Anthony R / Maus, Marcela V / Melenhorst, J Joseph / Pequignot, Edward / Ruella, Marco /

Shestov, Maksim / Byrd, John C / Schuster, Stephen J / Siegel, Donald L / Levine, Bruce L / June, Carl H / Porter, David L

Blood advances

2022 Volume 6, Issue 21, Page(s) 5774–5785

Abstract: In chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton's ... ...

Abstract	In chronic lymphocytic leukemia (CLL) patients who achieve a complete remission (CR) to anti-CD19 chimeric antigen receptor T cells (CART-19), remissions are remarkably durable. Preclinical data suggesting synergy between CART-19 and the Bruton's tyrosine kinase (BTK) inhibitor ibrutinib prompted us to conduct a prospective single-center phase 2 trial in which we added autologous anti-CD19 humanized binding domain T cells (huCART-19) to ibrutinib in patients with CLL not in CR despite ≥6 months of ibrutinib. The primary endpoints were safety, feasibility, and achievement of a CR within 3 months. Of 20 enrolled patients, 19 received huCART-19. The median follow-up for all infused patients was 41 months (range, 0.25-58 months). Eighteen patients developed cytokine release syndrome (CRS; grade 1-2 in 15 of 18 subjects), and 5 developed neurotoxicity (grade 1-2 in 4 patients, grade 4 in 1 patient). While the 3-month CR rate among International Working Group on CLL (iwCLL)-evaluable patients was 44% (90% confidence interval [CI], 23-67%), at 12 months, 72% of patients tested had no measurable residual disease (MRD). The estimated overall and progression-free survival at 48 months were 84% and 70%, respectively. Of 15 patients with undetectable MRD at 3 or 6 months, 13 remain in ongoing CR at the last follow-up. In patients with CLL not achieving a CR despite ≥6 months of ibrutinib, adding huCART-19 mediated a high rate of deep and durable remissions. ClinicalTrials.gov number, NCT02640209.
MeSH term(s)	Humans ; Antigens, CD19 ; Disease-Free Survival ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Neoplasm, Residual/drug therapy ; Prospective Studies ; Pyrazoles/therapeutic use ; Pyrimidines/therapeutic use ; T-Lymphocytes
Chemical Substances	Antigens, CD19 ; ibrutinib (1X70OSD4VX) ; Pyrazoles ; Pyrimidines
Language	English
Publishing date	2022-04-05
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022007317
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Article ; Online: Decade-long leukaemia remissions with persistence of CD4

Melenhorst, J Joseph / Chen, Gregory M / Wang, Meng / Porter, David L / Chen, Changya / Collins, McKensie A / Gao, Peng / Bandyopadhyay, Shovik / Sun, Hongxing / Zhao, Ziran / Lundh, Stefan / Pruteanu-Malinici, Iulian / Nobles, Christopher L / Maji, Sayantan / Frey, Noelle V / Gill, Saar I / Loren, Alison W / Tian, Lifeng / Kulikovskaya, Irina /

Gupta, Minnal / Ambrose, David E / Davis, Megan M / Fraietta, Joseph A / Brogdon, Jennifer L / Young, Regina M / Chew, Anne / Levine, Bruce L / Siegel, Donald L / Alanio, Cécile / Wherry, E John / Bushman, Frederic D / Lacey, Simon F / Tan, Kai / June, Carl H

Nature

2022 Volume 602, Issue 7897, Page(s) 503–509

Abstract: The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various ... ...

Abstract	The adoptive transfer of T lymphocytes reprogrammed to target tumour cells has demonstrated potential for treatment of various cancers
MeSH term(s)	Antigens, CD19/immunology ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/immunology ; Cell Separation ; Humans ; Immunotherapy, Adoptive ; Leukemia/immunology ; Leukemia/therapy ; Receptors, Chimeric Antigen/immunology ; Time Factors
Chemical Substances	Antigens, CD19 ; Receptors, Chimeric Antigen
Language	English
Publishing date	2022-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-04390-6
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