B7 homolog 3 in pancreatic cancer

Table 1 Preclinical studies involving B7 homolog 3-targeting agents in pancreatic cancer

Ref.	Agent/drug	Study models
Lutz et al[101]	Fc-optimized mAb B7-H3-SDIE	In vitro PDAC model
Kasten et al[103]	B7-H3-specific mAb 376.96 conjugated with 212Pb	PDAC in vitro and PDX models
Scribner et al[104] and Wittwer et al[105]	MGC0181 (alone or combined with an anti-PD-1 agent)	PC PDX and immunocompetent mouse models
Lutz et al[114]	B7-H3xCD3 bsAb CC-3	In vitro hepatic, gastric, and PDAC models
You et al[115]	B7-H3x4-1BB2 bsAb	In vitro models of PC and other solid tumors

¹Also known as vobramitamab duocarmazine, an antibody-drug conjugate comprised of a humanized B7 homolog 3 monoclonal antibody conjugated via a cleavable linker to the prodrug seco-duocarmycin hydroxybenzamide azaindole.

²Costimulatory receptor that belongs to the tumor necrosis factor receptor superfamily, broadly expressed on immune cells.

mAb: Monoclonal antibody; bsAb: Bispecific antibody; PC: Pancreatic cancer; PD-1: Programmed cell death protein 1; PDAC: Pancreatic ductal adenocarcinoma; PDX: Patient-derived xenograft; B7-H3: B7 homolog 3.

Table 2 Clinical studies involving B7 homolog 3-targeting agents in pancreatic cancer

Ref.	Agent/drug	Route of administration	Study participants	Status
NCT05293496, phase I[106]	Vobramitamab duocarmazine1 in combination with lorigerlimab2	Intravenous	Patients with relapsed or refractory, unresectable, locally advanced, or metastatic solid tumors including PC	Recruiting
NCT06330064, phase II[110]	I-DXD3	Intravenous	Patients with recurrent or metastatic solid tumors, including PDAC	Recruiting
NCT02628535, phase I[113]	Orlotamab4	Intravenous	Patients with unresectable or metastatic B7-H3-expressing neoplasms including PC	Terminated
NCT05143151, phase I/phase II[117]	CD276 CAR T cells	Intravenous	Adult patients with refractory PC	Recruiting
NCT06158139, phase I[118]	Ic9-CAR.B7-H3 T cells	Intravenous	Adult patients with refractory PDAC	Not yet recruiting

¹Also known as MGC018, an antibody-drug conjugate comprised of a humanized anti-B7 homolog 3 (B7-H3) monoclonal antibody (mAb) conjugated via a cleavable linker to the prodrug seco-duocarmycin hydroxybenzamide azaindole.

²Bispecific dual-affinity re-targeting (DART) molecule that targets both cytotoxic T lymphocyte-associated protein 4 and programmed cell death protein 1.

³B7-H3–directed antibody-drug conjugate consisting of anti-B7-H3 IgG1 mAb (MABX-9001a) and a payload, a potent DNA topoisomerase I inhibitor.

⁴CD3xB7-H3 DART protein also known as MGD009.

CAR: Chimeric antigen receptor; I-DXD: Ifinatamab deruxtecan; PC: Pancreatic cancer; PDAC: Pancreatic ductal adenocarcinoma; B7-H3: B7 homolog 3.