Table 3.

Blocking B7/CD28 family of molecules for tumor therapy

Molecule	Tumor model	Intervention	Result	Ref
CTLA-4	Mouse colon tumor (51BLim10)	Antibody blockade of CTLA-4	Tumor regression	[102]
	Mouse prostate tumor (TRAMP transgenic mice)	Antibody blockade of CTLA-4	Reduce tumor growth	[103]
		Tumor resection and antibody blockade of CTLA-4	Reduced metastatic relapse	[103]
		Vaccination with irradiated tumor cells and antibody blockade of CTLA-4	Reduce tumor incidence	[104]
		Vaccination with irradiated tumor cells expressing GMCSF and antibody blockade of CTLA-4	Reduce tumor incidence	[104]
	Mouse mamary carcinoma (SM1) b	Vaccination with irradiated tumor cells expressing GMCSF and antibody blockade of CTLA-4	Reduce tumor growth and regression	[105]
	Mouse melanoma (B16) c	Vaccination with irradiated tumor cells expressing GMCSF and antibody blockade of CTLA-4	Reduce tumor growth	[88]
		Depletion of CD25+ cells and vaccination with irradiated tumor cells expressing GMCSF and antibody blockade of CTLA-4.	Reduce tumor growth	[106]
	Mouse sarcoma (methA) d	Vaccination with vaccinia virus expressing p53 (rMVAp53) and antibody blockade of CTLA-4.	Tumor regression and increased survival	[107]
	Human metastatic melanoma	gp100 peptide vaccination and multiple rounds of antibody blockade of CTLA-4e.	4/29 patients respond (2 complete response and 2 partial response) 3/14 patients respond and autoimmune disease developed in 6/14 patients	[108], [109]
		Multiple-peptide vaccination and multiple rounds of antibody blockade of CTLA-4**.	7/19, no relapse	[110]
		Vaccination with irradiated tumor cells expressing GMCSF and multiple rounds of antibody blockade of CTLA-4	Tumor necrosis in 3/3 patients	[111]
		Previous vaccinated with DC engenired to express gp100 and MART-1; gp100, peptide plus IL-2 underwent multiple rounds of antibody blockade of CTLA-4	No tumor necrosis in 4/4 patients, 2 patients showed CD8+ infiltration	[111]
	Human metastatic Ovarian carcinoma	Vaccination with irradiated tumor cells expressing GMCSF and multiple rounds of antibody blockade of CTLA-4	Stabilization of CA125 in 2/2 patients.	[111]
PD1	Mouse mastocytoma f	Antibody blockade of PD1	Enhance antitumor immunity induced by vaccination in combination with T-cell therapy.	[78]
	Mouse subcutaneous and Hematogenous melanoma (B16)	Inoculation of B16 in PD-1 deficient mice and PD-1 transgenic mice	Decreased tumor growth Reduced tumor foci in the liver, increased CD8+ cells at the tumor site and enhanced effector function.	[112]
	Mouse colon cancer (CT26) g	Intravenous inoculation of CT26 in Balb/c PD-1 deficient mice	Decreased tumor growth.	[112]
	Mouse hepatoma (H22) h	Vaccination with plasmid encoding secondary lymphoid tissue chemokine (SLC) CCL21 and plasmid encoding the extracellular domain of PD-1	Reduced tumor size and increase survival.	[113]
PD-L1	Mouse mastocytoma f	-Transfectant expression of PD-L1 in P815. -Transfectant expression of PD-L1 in P815 expressing B71.	-Increased tumor resistance to anti CD137 (41BB) or CD8 specific killing or transfer therapy. -Increase tumor growth.	[77, 78, 114]
	Autologous human ovarian cancer grown in NOD-SCID mice	Antibody blockade of PD-L1	Enhanced MDC-mediatedi T-cell activation with upregulation of IL-2 and IFN-γ and reduced production of IL-10	[115]
	Mouse SCC (A14) j	-Transfectant expression of PD-L1 in A14. -T cell therapy with activated and non activated SCVII T cell clones and antibody blockade of PD-L1	Equal tumor growth. Increased survival only when activated SCVII T cell clones were used	[100]
	Mouse hematogenous melanoma (B16) c	Inoculation of B16 in the spleen of in B6 mice and treatment with anti PD-L1	Decreased tumor growth.	[112]
	Mouse colon cancer (CT26) g	Inoculation of CT26 in Balb/c mice and treatment with anti PD-L1	Decreased tumor growth.	[112]
B7-DC	Mouse colon cancer (CT26) g	Inoculation of CT26 in B7-DC deficient mice.	Reduced survival and increased foci in the liver. Decreased anti-tumor CD8 response.	[39]
B7-H3	Mouse lymphoma (EL-4) k	Intratumoral injection of a B7-H3 pcDNA3 expression plasmid.	Enhanced antitumor immunity mediated by CD8 and NK cells.	[83]
	Mouse mastocytoma (P815) f	Expression of B7-H3 in transfectant P815.	Enhanced antitumor CD8 response, slowed tumor growth and increased survival.	[84]

^aTRAM transgenic mice express SV40 T antigen transgene under the control of rat probasin promoter, which directs expression to prostatic epithelium in an androgen-regulated manner. TRAMP mice develop pathogenesis of neoplasia that mirrors that in man.)

^bSM1: BALB/C-derived mammary carcinoma

^cB16: C57BL/6-derived melanoma

^dMethylcholanthrene-induced sarcoma

^eThere are other studies not mentioned here in which anti-CTLA-4 therapy was used alone and only once with less success [111]

^fP815: Balb/c-derived mastocytoma.

^gCT26: Balb/c-derived colon cancer cell line.

^hH22 murine hepatoma, Balb/c derived

ⁱMDC: monocyte-derived dendritic cells

^jA14: C3H/HeN mice derived SCC.

^kEL-4: C57BL/6-derived thymoma