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Article ; Online: Embracing Myeloma Chimeric Antigen Receptor-T: From Scientific Design to Clinical Impact.

Hosoya, Hitomi / Rodriguez-Otero, Paula / Sidana, Surbhi / Borrello, Ivan M

American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting

2023 Volume 43, Page(s) e389860

Abstract: Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were ... ...

Abstract	Despite recent advancement of treatment strategies in multiple myeloma (MM), patients with relapsed/refractory MM disease, particularly after triple-class refractoriness, continue to have poor prognosis. Chimeric antigen receptor (CAR-T) cells were developed and applied to improve outcomes in this setting, and two products, idecabtagene vicleucel and ciltacabtagene autoleucel, both targeting B-cell maturation antigen, have been approved by the Food and Drug Administration in the United States and European Medicines Agency in Europe. Both have shown unprecedented clinical outcomes with high response rate and prolonged progression-free survival and overall survival in this patient population with grim prognosis. Currently, further investigations are ongoing for CAR-T targeting different tumor antigens such as G protein-coupled receptor, class C, group 5, member D or with different combinations of intracellular signaling domains, as well as fourth-generation CAR-T with antigen-unrestricted inducible cytokines. Although CAR-T therapies hold hopes and enthusiasm from the myeloma community, several hurdles remain before these treatments become available for all patients in need. These barriers include CAR-T-cell manufacturing availability, access to administering centers, financial cost, caregivers' availability, and socioeconomic and racial disparities. Expanding clinical trial eligibility criteria and real-world data collection and analysis is crucial to understand the efficacy and safety of CAR-T in the patient cohort who tends to be excluded from current trials.
MeSH term(s)	Humans ; Multiple Myeloma/therapy ; Receptors, Chimeric Antigen/genetics ; Immunotherapy, Adoptive ; Cytokines ; Europe
Chemical Substances	Receptors, Chimeric Antigen ; Cytokines
Language	English
Publishing date	2023-06-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2431126-1
ISSN	1548-8756 ; 1548-8748
ISSN (online)	1548-8756
ISSN	1548-8748
DOI	10.1200/EDBK_389860
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Article: Tumor-Specific CD8

Zawidzka, Elizabeth M / Biavati, Luca / Thomas, Amy / Zanettini, Claudio / Marchionni, Luigi / Leone, Robert / Borrello, Ivan

bioRxiv : the preprint server for biology

2023

Abstract: Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating ... ...

Abstract	Immunotherapy is now an integral aspect of cancer therapy. Strategies employing adoptive cell therapy (ACT) have seen the establishment of chimeric antigen receptor (CAR)-T cells using peripheral blood lymphocytes as well as tumor infiltrating lymphocytes (TILs) with significant clinical results. Despite these successes, the limitations of the current strategies are also emerging and novel approaches are needed. The bone marrow (BM) is an immunological niche that houses T cells with specificity for previously encountered antigens, including tumor-associated antigens from certain solid cancers. This study sought to improve our understanding of tumor-specific BM T cells in the context of solid tumors by comparing them with TILs, and to assess whether there is a rationale for using the BM as a source of T cells for ACT against solid malignancies. Herein, we demonstrate that T cells from the BM appear superior to TILs as a source of cells for cellular therapy. Specifically, they possess a memory-enriched phenotype and exhibit improved effector function, greater persistence within a tumor-bearing host, and the capacity for increased tumor infiltration. Taken together, these data provide a foundation for further exploring the BM as a source of tumor-specific T cells for ACT in solid malignancies.
Language	English
Publishing date	2023-08-29
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.08.28.555119
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Article ; Online: Marrow Infiltrating Lymphocytes: Their Role in Adoptive Immunotherapy.

Noonan, Kimberly A / Borrello, Ivan M

Cancer journal (Sudbury, Mass.)

2015 Volume 21, Issue 6, Page(s) 501–505

Abstract: The clinical results achieved with immunotherapy in the past few years have now firmly established it within the cancer armamentarium. Our group has explored a novel approach to adoptive T-cell therapy utilizing marrow-infiltrating lymphocytes (MILs) ... ...

Abstract	The clinical results achieved with immunotherapy in the past few years have now firmly established it within the cancer armamentarium. Our group has explored a novel approach to adoptive T-cell therapy utilizing marrow-infiltrating lymphocytes (MILs) initially developed with the concept of utilizing a population of T cells with a higher endogenous tumor specificity. Marrow-infiltrating lymphocytes are antigen-experienced T cells that home to and remain in the bone marrow (BM) because of the unique biology of the BM microenvironment. Marrow-infiltrating lymphocytes can easily be obtained from the BM and can be expanded to demonstrate enhanced antigen specificity. Current clinical trials utilize MILs for patients with myeloma as well as patients with relapsed disease following an allogeneic transplant. Ongoing preclinical work is currently evaluating MILs for use in solid cancers as well as pediatric cancers. The examination of a MIL as a source cell for chimeric antigen receptor T or transgenic cell receptor is also in the preclinical stages. Until now, for both chimeric antigen receptor T-cell therapy and transgenic cell receptor T-cell therapy, the target cell of choice has included peripheral blood. The unique antigen-experienced properties of MILs may make them the ideal source of cell for gene modification strategies. Therefore, MILs are a distinctive set of T cells that have been shaped by the unique BM microenvironment and may play a future role as a novel immunotherapy for hematologic malignancies.
MeSH term(s)	Bone Marrow/pathology ; Humans ; Immunotherapy, Adoptive/methods ; Lymphocytes, Tumor-Infiltrating/immunology
Language	English
Publishing date	2015-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2018400-1
ISSN	1540-336X ; 1528-9117 ; 1081-4442
ISSN (online)	1540-336X
ISSN	1528-9117 ; 1081-4442
DOI	10.1097/PPO.0000000000000159
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Zs.A 4470: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: A phase 1b study of dual PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory lymphoid malignancies.

Armand, Philippe / Lesokhin, Alexander / Borrello, Ivan / Timmerman, John / Gutierrez, Martin / Zhu, Lili / Popa McKiver, Mihaela / Ansell, Stephen M

Leukemia

2020 Volume 35, Issue 3, Page(s) 777–786

Abstract: Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with ... ...

Abstract	Simultaneously targeting other pathways could increase the activity of PD-1 blockade in lymphoid malignancies not sensitive to single-agent blockade. We explored the safety and efficacy of combined PD-1 and CTLA-4 or KIR blockade in patients with relapsed/refractory (R/R) lymphoid malignancies. This phase 1b trial enrolled adult patients with R/R classical Hodgkin lymphoma (cHL), non-Hodgkin lymphoma (NHL), or multiple myeloma (MM). Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. The primary endpoint was safety and tolerability, while secondary endpoints included overall (ORR) and CR rates (CRR), progression-free and overall survival. Sixty-five patients were treated with nivo/ipi, and 72 with nivo/liri. Twenty-nine percent of patients experienced grade 3-4 treatment-related adverse events with nivo/ipi, and 15% with nivo/liri. In cHL, ORR was 74% for nivo/ipi and 76% for nivo/liri, CRRs were 23% and 24%, respectively. In B-NHL and T-NHL, ORR range was 9-22% and CRR was 0-6%. No patient with MM had an objective response. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Alkaloids/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biomarkers, Tumor/genetics ; Biomarkers, Tumor/metabolism ; CTLA-4 Antigen/antagonists & inhibitors ; Drug Resistance, Neoplasm/drug effects ; Female ; Follow-Up Studies ; Hodgkin Disease/drug therapy ; Hodgkin Disease/pathology ; Humans ; Ipilimumab/administration & dosage ; Lymphoma, Non-Hodgkin/drug therapy ; Lymphoma, Non-Hodgkin/pathology ; Male ; Middle Aged ; Multiple Myeloma/drug therapy ; Multiple Myeloma/pathology ; Neoplasm Recurrence, Local/drug therapy ; Neoplasm Recurrence, Local/pathology ; Nivolumab/administration & dosage ; Prognosis ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Receptors, KIR/antagonists & inhibitors ; Salvage Therapy ; Survival Rate ; Young Adult
Chemical Substances	Alkaloids ; Biomarkers, Tumor ; CTLA-4 Antigen ; CTLA4 protein, human ; Ipilimumab ; PDCD1 protein, human ; Programmed Cell Death 1 Receptor ; Receptors, KIR ; Nivolumab (31YO63LBSN) ; lirinidine (54383-28-7)
Language	English
Publishing date	2020-06-29
Publishing country	England
Document type	Clinical Trial, Phase I ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	807030-1
ISSN	1476-5551 ; 0887-6924
ISSN (online)	1476-5551
ISSN	0887-6924
DOI	10.1038/s41375-020-0939-1
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Zs.A 2295: Show issues

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Article ; Online: A randomized, phase II trial of adjuvant immunotherapy with durable TKI-free survival in patients with chronic phase CML.

Webster, Jonathan A / Robinson, Tara M / Blackford, Amanda L / Warlick, Erica / Ferguson, Anna / Borrello, Ivan / Zahurak, Marianna / Jones, Richard J / Smith, B Douglas

Leukemia research

2021 Volume 111, Page(s) 106737

Abstract: Purpose: Chronic myeloid leukemia (CP-CML) patients can achieve undetectable minimal residual disease (UMRD) and discontinue tyrosine kinase inhibitors (TKIs). Cellular immunity plays an important role in CML disease control. We conducted a randomized, ... ...

Abstract	Purpose: Chronic myeloid leukemia (CP-CML) patients can achieve undetectable minimal residual disease (UMRD) and discontinue tyrosine kinase inhibitors (TKIs). Cellular immunity plays an important role in CML disease control. We conducted a randomized, non-blinded phase II trial of adjuvant immunotherapy with TKIs to facilitate TKI discontinuation. Methods: TKI-treated patients with CP-CML were randomized to receive the K562/GM-CSF vaccine (vaccine) OR Interferon-α + Sargramostim (IFN). If UMRD was achieved, then all treatment was stopped. Patients who did not achieve UMRD within one year, had a molecular relapse, or discontinued therapy for toxicity could crossover. Results: Thirty-four patients were randomized to IFN (n = 18) or vaccine (n = 16), and 21 patients crossed over (IFN⟶vaccine: n = 9, vaccine⟶IFN, n = 12). TKIs at enrollment included imatinib (n = 31), nilotinib (n = 2), and dasatinib (n = 1). No patients discontinued vaccine due to side effects, while 33 % of IFN-treated patients discontinued treatment. More patients randomized to IFN (47.4 %, 95 % CI: 16.7-66.7 %) versus vaccine (25.0 %, 95 % CI: 0.5-43.5 %) achieved UMRD within one year. Seven patients randomized to IFN discontinued treatment with 28.6 % (95 % CI: 8.9-92.2 %) sustaining treatment-free remission (TFR) at 1 year, while three patients randomized to vaccine discontinued treatment with none sustaining TFR. Including crossover, there was a cumulative discontinuation success rate of 36.4 % (95 % CI: 16.6 %-79.5 %) after adjuvant IFN. Patients who sustained TFR received a median of 29 months of imatinib prior to discontinuation. Conclusion: Adjuvant IFN led to durable TFRs with limited prior TKI exposure with comparable success to prior discontinuation trials, but many patients stopped IFN early.
MeSH term(s)	Adjuvants, Immunologic/administration & dosage ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Cancer Vaccines/administration & dosage ; Cross-Over Studies ; Dasatinib/administration & dosage ; Female ; Follow-Up Studies ; Humans ; Imatinib Mesylate/administration & dosage ; Immunotherapy/mortality ; Interferons/administration & dosage ; Leukemia, Myeloid, Chronic-Phase/drug therapy ; Leukemia, Myeloid, Chronic-Phase/immunology ; Leukemia, Myeloid, Chronic-Phase/mortality ; Leukemia, Myeloid, Chronic-Phase/pathology ; Male ; Middle Aged ; Prognosis ; Pyrimidines/administration & dosage ; Survival Rate ; Young Adult
Chemical Substances	Adjuvants, Immunologic ; Cancer Vaccines ; Pyrimidines ; Imatinib Mesylate (8A1O1M485B) ; Interferons (9008-11-1) ; nilotinib (F41401512X) ; Dasatinib (RBZ1571X5H)
Language	English
Publishing date	2021-11-02
Publishing country	England
Document type	Clinical Trial, Phase II ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	752396-8
ISSN	1873-5835 ; 0145-2126
ISSN (online)	1873-5835
ISSN	0145-2126
DOI	10.1016/j.leukres.2021.106737
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Zs.A 1321: Show issues

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Article ; Online: Mismatched donor transplantation with post-transplantation cyclophosphamide for advanced cutaneous T-cell lymphoma: a single-center retrospective study.

Leukemia & lymphoma

2022 Volume 63, Issue 12, Page(s) 2987–2991

MeSH term(s)	Humans ; Retrospective Studies ; Cyclophosphamide/adverse effects ; Graft vs Host Disease ; Lymphoma, T-Cell, Cutaneous/drug therapy ; Hematopoietic Stem Cell Transplantation ; Transplantation Conditioning
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-08-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2105330
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Zs.A 2997: Show issues

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Article ; Online: An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission.

Biavati, Luca / Huff, Carol Ann / Ferguson, Anna / Sidorski, Amy / Stevens, M Amanda / Rudraraju, Lakshmi / Zucchinetti, Cristina / Ali, Syed Abbas / Imus, Philip / Gocke, Christian B / Gittelman, Rachel M / Johnson, Sarah / Sanders, Catherine / Vignali, Marissa / Gandhi, Anita / Ye, Xiaobu / Noonan, Kimberly A / Borrello, Ivan

Clinical cancer research : an official journal of the American Association for Cancer Research

2021 Volume 27, Issue 24, Page(s) 6696–6708

Abstract: ... as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical ...

Abstract	Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MM-GVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). Patients and methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. Results: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27 Conclusions: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating M-spike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.
MeSH term(s)	Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; CD8-Positive T-Lymphocytes ; Cancer Vaccines ; Granulocyte-Macrophage Colony-Stimulating Factor ; Hematopoietic Stem Cell Transplantation ; Humans ; Lenalidomide ; Multiple Myeloma/drug therapy ; Neoplasm Recurrence, Local/drug therapy
Chemical Substances	Cancer Vaccines ; Granulocyte-Macrophage Colony-Stimulating Factor (83869-56-1) ; Lenalidomide (F0P408N6V4)
Language	English
Publishing date	2021-10-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-21-1916
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Zs.A 4223: Show issues

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Article ; Online: Allogeneic Blood or Marrow Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Acute Lymphoblastic Leukemia in Patients Age ≥55 Years.

Webster, Jonathan A / Reed, Madison / Tsai, Hua-Ling / Ambinder, Alexander / Jain, Tania / Dezern, Amy E / Levis, Mark J / Showel, Margaret M / Prince, Gabrielle T / Hourigan, Christopher S / Gladstone, Douglas E / Bolanos-Meade, Javier / Gondek, Lukasz P / Ghiaur, Gabriel / Dalton, W Brian / Paul, Suman / Fuchs, Ephraim J / Gocke, Christian B / Ali, Syed Abbas /

Huff, Carol Ann / Borrello, Ivan M / Swinnen, Lode / Wagner-Johnston, Nina / Ambinder, Richard F / Luznik, Leo / Gojo, Ivana / Smith, B Douglas / Varadhan, Ravi / Jones, Richard J / Imus, Philip H

Transplantation and cellular therapy

2022 Volume 29, Issue 3, Page(s) 182.e1–182.e8

Abstract: Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of ... ...

Abstract	Patients age ≥55 years with acute lymphoblastic leukemia (ALL) fare poorly with conventional chemotherapy, with a 5-year overall survival (OS) of ∼20%. Tyrosine kinase inhibitors and novel B cell-targeted therapies can improve outcomes, but rates of relapse and death in remission remain high. Allogeneic blood or marrow transplantation (alloBMT) provides an alternative consolidation strategy, and post-transplantation cyclophosphamide (PTCy) facilitates HLA-mismatched transplantations with low rates of nonrelapse mortality (NRM) and graft-versus-host disease (GVHD). The transplantation database at Johns Hopkins was queried for patients age ≥55 years who underwent alloBMT for ALL using PTCy. The database included 77 such patients. Most received reduced-intensity conditioning (RIC) (88.3%), were in first complete remission (CR1) (85.7%), and had B-lineage disease (90.9%). For the entire cohort, 5-year relapse-free survival (RFS) and overall survival (OS) were 46% (95% confidence interval [CI], 34% to 57%) and 49% (95% CI, 37% to 60%), respectively. Grade III-IV acute GVHD occurred in only 3% of patients, and chronic GVHD occurred in 13%. In multivariable analysis, myeloablative conditioning led to worse RFS (hazard ratio [HR], 4.65; P = .001), whereas transplantation in CR1 (HR, .30; P = .004) and transplantation for Philadelphia chromosome-positive (Ph
MeSH term(s)	Humans ; Middle Aged ; Bone Marrow ; Cyclophosphamide/therapeutic use ; Hematopoietic Stem Cell Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy ; Graft vs Host Disease/drug therapy ; Recurrence ; Acute Disease
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2022-12-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2022.12.018
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Zs.A 5082: Show issues

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Article ; Online: Allogeneic Blood or Marrow Transplantation with Nonmyeloablative Conditioning and High-Dose Cyclophosphamide-Based Graft-versus-Host Disease Prophylaxis for Secondary Central Nervous System Lymphoma.

Sterling, Cole H / Tsai, Hua-Ling / Holdhoff, Matthias / Bolaños-Meade, Javier / Luznik, Leo / Fuchs, Ephraim J / Huff, Carol Ann / Gocke, Christian B / Ali, Syed Abbas / Borrello, Ivan M / Varadhan, Ravi / Jones, Richard J / Gladstone, Douglas E / Ambinder, Richard F / Wagner-Johnston, Nina / Swinnen, Lode J / Imus, Philip H

Transplantation and cellular therapy

2021 Volume 27, Issue 10, Page(s) 863.e1–863.e5

Abstract: Secondary central nervous system (CNS) lymphoma is a rare and often fatal complication of non-Hodgkin lymphoma (NHL). Treatment options include radiation therapy, high-dose systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with ... ...

Abstract	Secondary central nervous system (CNS) lymphoma is a rare and often fatal complication of non-Hodgkin lymphoma (NHL). Treatment options include radiation therapy, high-dose systemic chemotherapy, intrathecal chemotherapy, and high-dose chemotherapy with autologous stem cell rescue, but outcomes remain poor. Allogeneic blood or marrow transplantation (alloBMT) is widely used in patients with relapsed/refractory systemic NHL. We sought to understand whether a graft-versus-lymphoma effect could maintain remission in CNS disease. We reviewed outcomes in 20 consecutive patients with secondary CNS lymphoma who underwent alloBMT with nonmyeloablative conditioning using fludarabine, cyclophosphamide, and 200 cGy total body irradiation. For graft-versus-host disease prophylaxis, all patients received post-transplantation cyclophosphamide, mycophenolate mofetil, and a calcineurin inhibitor. With a median follow up of 4.1 years, the median overall survival for the entire cohort was not reached. Median progression-free survival was 3.8 years (95% confidence interval [CI], 5.3 months to not reached). The cumulative incidence of relapse was 25% (95% CI, 5% to 45%), and nonrelapse mortality was 30% (95% CI, 5% to 54%) at 4 years. Of the 5 patients who relapsed, 2 were CNS only, 1 was systemic only, and 2 were combined CNS/systemic. The use of alloBMT in CNS lymphoma merits further investigation.
MeSH term(s)	Bone Marrow ; Central Nervous System ; Cyclophosphamide/therapeutic use ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma/therapy ; Neoplasm Recurrence, Local
Chemical Substances	Cyclophosphamide (8N3DW7272P)
Language	English
Publishing date	2021-07-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.07.015
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Article ; Online: Bifunctional immune checkpoint-targeted antibody-ligand traps that simultaneously disable TGFβ enhance the efficacy of cancer immunotherapy

Rajani Ravi / Kimberly A. Noonan / Vui Pham / Rishi Bedi / Alex Zhavoronkov / Ivan V. Ozerov / Eugene Makarev / Artem V. Artemov / Piotr T. Wysocki / Ranee Mehra / Sridhar Nimmagadda / Luigi Marchionni / David Sidransky / Ivan M. Borrello / Evgeny Izumchenko / Atul Bedi

Nature Communications, Vol 9, Iss 1, Pp 1-

2018 Volume 14

Abstract: Antitumor T cells can be inhibited by a TGFβ rich tumor microenvironment. The authors develop bifunctional proteins comprising CTLA-4 or PD-L1 immune checkpoint-targeted antibodies fused to a “TGFβ trap” and show that they counteract tumor immune ... ...

Abstract	Antitumor T cells can be inhibited by a TGFβ rich tumor microenvironment. The authors develop bifunctional proteins comprising CTLA-4 or PD-L1 immune checkpoint-targeted antibodies fused to a “TGFβ trap” and show that they counteract tumor immune tolerance and enhance the efficacy of these antibodies.
Keywords	Science ; Q
Language	English
Publishing date	2018-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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