Skip to main content

Table 3 Inhibitors and antibodies targeting the adaptive immune system in the TME for cancer therapy used in clinical trials or approved by the FDA. Data has been collected from http://www.fda.gov, and http://www.clinicaltrials.gov accessed in November 2023

From: Harnessing the tumor microenvironment: targeted cancer therapies through modulation of epithelial-mesenchymal transition

Drugs targeting the adaptive immune system in the TME

Targeting T-Cells

Targeted Molecule

Drug Name

Type of Agent/s

Mechanism of Action

Status

Cancer Type/s

NCTs

References

PD-1

Spartalizumab

Neutralizing antibodies

Bind to PD-1 receptor and suppress its interaction with PD-L1/PD-L2, releasing PD-1 pathway-induced inhibition of anticancer response

Phase 2

ASTs

NCT02605967

PMID: 34,433,653

Nivolumab

Approved

ASTs (CRC, EC, GC, HCC, HNSCC, MEL, MES, NSCLC, RCC, UC), HL

NCT01721772 (ASTs), NCT02181738 (HL)

PMID: 25,399,552 (AST), PMID: 28,438,889 (HL)

Pembrolizumab

Approved

ASTs (BC, CC, EC, EMC, GC, MCC, MEL, HCC, HNSSC, NSCLC, RCC, SCC, UC), HL

NCT01866319 (ASTs), NCT02684292 (HL)

PMID: 25,891,173 (AST), PMID: 33,721,562 (HL)

Cemiplimab

Approved

ASTs (BCC, cSSC, NSCLC)

NCT02760498

PMID: 29,863,979

PD-L1

Atezolizumab

Neutralizing antibodies

Bind to PD-L1 to block the interaction between PD-1 and PD-L1, restoring anticancer T-cell function

Approved

ASTs (ASPS, HCC, MEL, NSCLC, SCLC, TNBC, UC)

NCT02108652

PMID: 30,541,754

Avelumab

Approved

ASTs (MCC, RCC, UC)

NCT02155647

PMID: 29,566,106

Durvalumab

Approved

ASTs (BTC, HCC, NSCLC, SCLC)

NCT02125461

PMID: 28,885,881

CTLA4

Ipilimumab

Neutralizing antibody

Blocks the inhibitory signal of CTLA4, allowing cytotoxic T-cells to kill cancer cells

Approved

ASTs (CRC, HCC, MEL, MES, RCC, NSCLC)

NCT00094653

PMID: 20,525,992

TIGIT

BMS-986207

Blocking antibodies

Bind to TIGIT to prevent interaction with its ligands

    

Phase 2

ASTs

NCT02913313

PMID: 34,572,463

   

Tiragolumab

  

Phase 2

ASTs

NCT03563716

PMID: 35,576,957

AB154

  

Phase 3

ASTs

NCT05568095

PMID: 38,724,599

Vibostolimab

  

Phase 3

ASTs (MEL)

NCT05665595

PMID: 37,410,978

TIM3

Sym023

Antagonistic antibodies

Bind to TIM3 expressed on specific T-cells including TILs, thereby averting T-cell inhibition

Phase 1

ASTs

NCT03489343

PMID: 38,721,404

 

LY3321367

  

Phase 1

ASTs

NCT03099109

PMID: 33,514,524

 

BMS-986258

  

Phase 2

ASTs

NCT03446040

PMID: 33,407,992

 

INCAGN02390

  

Phase 1

ASTs

NCT03652077

PMID: 37,670,328

 

Cobolimab

  

Phases 3

NSCLC

NCT04655976

PMID: 38,730,635

 

MBG453

  

Phase 3

LEU (CMML), MDS

NCT04266301

PMID: 37,083,373

LAG3

FS118

Blocking and antagonistic

     

bispecific antibodies

Block MHC-II–LAG3

      

interaction

Phase 2

ASTs

NCT03440437

PMID: 36,342,102

   
 

LAG525

  

Phase 2

ASTs

NCT02460224

PMID: 35,217,575

 

IMP321

  

Phase 1

ASTs

NCT03252938

PMID: 37,742,484

 

Fianlimab

  

Phase 3

ASTs (MEL)

NCT05352672

PMID: 37,004,702

 

Relatlimab

  

Approved

ASTs (MEL)

NCT03470922

PMID: 34,986,285

OX40

MOXR0916

Agonist antibody

Binds and activates OX40

Phase 1

ASTs

NCT02219724

PMID: 35,699,599

ICOS

Vopratelimab

Agonist antibody

Binds and activates ICOS

Phase 2

ASTs

NCT02904226

PMID: 35,511,938

VISTA

CA-170

Small-molecule VISTA/PD-L1 antagonist

Rescues the effector functions of T-cells inhibited by VISTA and PD-L1/PD-L2

Phase 1

ASTs

NCT02812875

PMID: 34,103,659

Targeting B-Cells

       

Targeted Molecule

Drug Name

Type of Agent/s

Mechanism of Action

Status

Cancer Type/s

NCTs

References

BCR

Acalabrutinib

Small-molecule inhibitors

Inhibit the BTK preventing the activation of BCR signaling pathway, which in turn impedes B-cell activation and BTK-mediated induction of downstream survival pathways

Approved

LEU (CLL, SLL), MCL

NCT02477696 (LEU), NCT02213926 (MCL)

PMID: 34,310,172 (LEU), PMID: 29,241,979 (MCL)

 

Ibrutinib

  

Approved

LEU (CLL, SLL), WM

NCT02477696 (LEU), NCT02165397 (WM)

PMID: 34,310,172 (LEU), PMID: 34,606,378 (WM)

  1. Targeted Molecules: BCR: B-cell receptor; CTLA4: Cytotoxic T lymphocyte-associated protein-4; ICOS: Inducible T-cell co-stimulatory; LAG-3: Lymphocyte activation gene-3; OX40: OX40 receptor or tumor necrosis factor receptor superfamily, member 4 (TNFRSF4); PD-1: Programmed cell death protein 1; PD-L1: Programmed death-ligand 1; TIGIT: T-cell immunoreceptor with Ig and ITIM domains; TIM-3: T-cell immunoglobulin and mucin-domain containing-3; VISTA: V-domain Ig suppressor of T cell activation. Cancer Types: ASPS: Alveolar Soft Part Sarcoma; ASTs: Advanced Solid Tumors; BC: Breast Cancer; BCC: Basal Cell Carcinoma; BTC: Biliary Tract Cancer; CC: Cervical Cancer; CLL: Chronic Lymphocytic Leukemia; CMML: Chronic myelomonocytic leukemia; CRC: Colorectal Cancer; cSCC: Cutaneous Squamous Cell Carcinoma; EC: Esophageal Carcinoma; EMC: Endometrial Cancer; GC: Gastric Cancer; HCC: Hepatocellular Carcinoma; HL: Hodgkin's Lymphoma; HNSCC: Head and Neck Squamous Cell Carcinoma; LEU: Leukemia; MCC: Merkel Cell Carcinoma; MCL: Mantle Cell Lymphoma; MDS: Myelodysplastic syndrome; MEL: Melanoma; MES: Mesothelioma; NSCLC: Non-Small Cell Lung Cancer; RCC: Renal Cell Carcinoma; SCC: Squamous Cell Carcinoma; SCLC: Small Cell Lung Cancer; SLL: Small Lymphocytic Leukaemia; TNBC: Triple-Negative Breast Cancer; UC: Urothelial Carcinoma; WM: Waldenström’s macroglobulinemia. In case drugs targeting the adaptive immune system in the TME for cancer therapy are being used in several ASTs, only a representative clinical trial (NCT) and its related reference (PMID) have been selected for (a) specific AST(s)
Back to article page

Journal of Hematology & Oncology

ISSN: 1756-8722

Contact us