Hurdles to breakthrough in CAR T cell therapy of solid tumors

Marofi, Faroogh; Achmad, Harun; Bokov, Dmitry; Abdelbasset, Walid Kamal; Alsadoon, Zeid; Chupradit, Supat; Suksatan, Wanich; Shariatzadeh, Siavash; Hasanpoor, Zahra; Yazdanifar, Mahboubeh; Shomali, Navid; Khiavi, Farhad Motavalli

doi:10.1186/s13287-022-02819-x

Stem Cell Research & Therapy

Table 2 Summary of clinical trials exploiting the improvement strategy to overcoming CAR T cell challenges in solid tumors (from clinicalTrials.gov)

From: Hurdles to breakthrough in CAR T cell therapy of solid tumors

Improving plan	Strategy	CAR T design	NCT number	Tumor type
Immune checkpoint inhibition	Expressing immune checkpoint antibodies	Anti-CTLA-4/PD-1 expressing MUC1-CAR-T	NCT03179007	Advanced Solid tumor
	Use CRISPR-Cas9 to knocked out the PD-1 gene	Mesothelin-directed CAR-T cells	NCT03747965	Solid Tumor, Adult
	Secretion of anti-PD-L1 scFv	Autologous aPD-L1 armored anti-CD22 CAR T cells	NCT04556669	Solid Tumor, Adult
				Cervical Cancer
				Sarcoma, NSCLC
	Secreting PD-1 nanobodies	αPD1-MSLN-CAR T cells	NCT04503980	Colorectal Cancer
				Ovarian Cancer
	Pembrolizumab	CART-EGFRvIII T cells	NCT03726515	Glioblastoma
	Ipilimumab,	IL13Rα2-Targeted CAR-T Cells	NCT04003649	Recurrent Glioblastoma
	Nivolumab			Refractory Glioblastoma
Cytokine secretion	IL-15	Glypican-3-specific CAR-T Cells	NCT04377932	Liver Cancer, Wilms Tumor, Yolk Sac Tumor, Liposarcoma, and 2 more
	IL-15 and IL-21	Glypican-3-specific CAR-T Cells	NCT04715191	Liver Cancer, Wilms Tumor, Yolk Sac Tumor, Liposarcoma, and 2 more
	IL-12	4H11-28z/fIL-12/EGFRt + Genetically-modified T cells	NCT02498912	Solid Tumors
Lymphodepletion	Cyclophosphamide	Anti-GD2-CAR engineered T cells	NCT02107963	Sarcoma, Osteosarcoma
				Neuroblastoma, Melanoma
	Fludarabine, Cyclophosphamide	Retroviral vector-transduced autologous T cells to express anti-GPC3 CARs	NCT03084380	Hepatocellular Carcinoma
Transient CAR expression	RNA electroporation	T cells modified with RNA anti -cMET CAR	NCT03060356	Malignant Melanoma,
				Breast Cancer
Diminishing toxicity and CRS	AP1903	Anti-GD2-CAR engineered T cells	NCT02107963	Sarcoma, Osteosarcoma
				Neuroblastoma, Melanoma
	Metoprolol, a beta-blocker	CAR T cells	NCT04082910	Solid Tumor,
				Hematological Malignancy
	Inducible caspase 9 safety switch	iC9.GD2.CAR.IL-15 T-cells	NCT03721068	Neuroblastoma,
				Osteosarcoma
Improving cell proliferation and persistence	Aldesleukin	Anti-hCD70 CAR transduced PBL	NCT02830724	Pancreatic Cancer, Renal Cell Cancer, Breast Cancer
				Melanoma, Ovarian Cancer
	Rimiducid (improved by activating the iMC)	PSCA-Targeted CAR-T Cells (BPX-601)	NCT02744287	Metastatic Prostate Cancer
				Metastatic Pancreatic Adenocarcinoma, and 3 more

Programmed cell death protein 1 (PD1), Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), Mucin 1 (MUC1), Clustered regularly interspaced short palindromic repeats (CRISPR), CRISPR-associated protein 9 (Cas9), Single chain variable fragment (scFv), Non-small cell lung cancer (NSCLC), Mesothelin (MSLN), Epidermal growth factor receptor variant III (EGFRvIII), Glypican-3 (GPC3), Inducible caspase 9 (iC9), Peripheral blood lymphocytes (PBL), Prostate stem cell antigen (PSCA)

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ISSN: 1757-6512

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