Current status of antigen-specific T-cell immunotherapy for advanced renal-cell carcinoma

Figures & data

Table 1. RCC antigens recognized by spontaeously arising tumor-reactive CD8 CTL clones

Gene	HLA restriction	Peptide sequence	Antigenic modulation	Expession on normal tissue	Shared antigenicity	T-cell origin	Reference
HLA-A*02	HLA-A*02	n/a	point mutation	Not on PBL	No	RCC TIL	13
HSP70–2	HLA-A*02	SLFEGIDIYT	point mutation	No	No	RCC TIL	14
RAGE1	HLA-B7	SPSSNRIRNT	n/a	Retina	Yes, 1.7% RCC cases	RCC TIL	15
RU1	HLA-B*51	VPYGSFKHV	alternative cleavage	Unknown	Shared cytotoxicity against melanoma	RCC PBL	16
M-CSF	HLA-B*3501	LPAVVGLSPGEQEY	alternative ORF	Kidney and liver	Yes	RCC TIL	17
iCE	HLA-B*0702	SPRWWPTCL	alternative ORF	Unknown	Yes	RCC TIL	18
RU2	HLA-B7	LPRWPPPQL	antisense transcript	Kidney, liver,testies, and bladders	Yes, 100% RCC cases	RCC PBL	19
FGF-5	HLA-A*03	NTYASPRFK	post-translational splicing	Kidney and brain	Yes	RCC TIL	20

Abbreviations: HLA – human leukocyte antigen; TIL – tumor-infiltrating lymphocyte; PBL – peripheral blood leukocyte; n/a – not applicable; ORF – open reading frame

Figure 1. RCC has a high objective response rate to immune checkpoint blockade despite low TMB. Median number of coding somatic mutations per megabase (MB) of DNA for 27 tumor types is plotted in log scale versus objective response rates for patients who received PD-1 or PD-L1 inhibitors as described in published studies. RCC is within the top 25% of objective response rates while being within the bottom 33% of median number of coding somatic mutations per MB. MMRd denotes mismatch repair-deficient, MMRp mismatch repair proficient, and NSCLC non-small cell lung cancer. Reproduced from Yarchoan, Hopkins & Jaffee⁵⁵ with copyright permission

Table 2. Clinical testing of single antigen-specific vaccination or T-cell engaging therapy for advanced RCC

Immune Target	Antigen Formulation	Adjuvant	HLA restriction	Combination therapy	Phase	Enrollment		Cellular Immune Response	Clinical Outcome	Reference
						Key Criteria	N
CAIX	3 HLA class I synthetic peptides	Montanide ISA-51	HLA-A*24	None	I	cytokine-refractory ccRCC	N = 23	Peptide reactive CTL response in 16/21 (76%) patients	3/23 PR (13%); lung metastases	74
	1 HLA class I plus 1 HLA class II synthetic peptide loaded on DC	keyhole limpet hemocyanin (KLH)	HLA-A*02 and HLA-DR	None	I	cytokine-refractory ccRCC	N = 8	No CTL response detected	No objective responses	75
	CAR T	None	not restricted	SQ IL-2	I/II	TKI or cytokine-refractory ccRCC	N = 12	Post infusion persistence < 5 weeks	No objective responses	76
VEGF-R1	1 HLA class I synthetic peptide per patient; matched to HLA expression	Montanide ISA-51VG	HLA-A*02:01 or *24:02	None	I	TKI or cytokine-refractory ccRCC	N = 18	Peptide reactive CTL response in 15/18 (83%) patients	2/18 PR (11%); lung and bone metastases	77
Hypoxia-inducible protein 2	1 HLA class I synthetic peptide	Montanide ISA-51VG	HLA-A*0201 or A*0206	None	I	TKI or cytokine-refractory RCC	N = 9	Peptide reactive CTL response in 8/9 (89%) patients	No objective responses	78
mutant VHL	1 HLA class I patient-specific synthetic peptide	Montanide ISA-51	mutant peptide selected based on autologous HLA motif	None	I	ccRCC expressing non-synonymous mutated VHL gene	N = 6	Peptide reactive CTL response in 4/5 (80%) patients	No objective responses	79
5T4 (trophoblast glycoprotein, TPBG)	Recombinant MVA expressing 5T4 (MVA-5T4; TroVax)	None	Not restricted	Low-dose IL-2	II	metastatic clear cell or papillary RCC	N = 25	8/18 (45%) 5T4-specific ELISPOT;	2 CR, 1 PR (12%)	80
				High-dose IL-2	II	metastatic clear cell or papillary RCC	N = 25	13/23 (56%) 5T4-specific CD8 + T-cell response	3 tumor regressions (12%) rendered disease free with surgery	81
				IFN-α	I/II	metastatic clear cell or papillary RCC; no prior systemic therapy	N = 11	5/11 (45%) 5T4-specific ELISPOT;	No objective responses	82
				None or IFN-α	II	treatment refractory metastatic clear cell or papillary RCC	N = 28	7/21 (33%) 5T4-specific ELISPOT;	1 PR (4%)	83
				Sunitinib, IL-2, or IFN-α	III (TRIST)	metastatic ccRCC; no prior systemic therapy	MVA-5T4 (n = 365) or placebo (n = 368)	Not evaluated	Primary endpoint OS was not increased; Median OS 20.1 (MVA-5T4) vs 19.2 mo (placebo); HR 1.07 (P = 0.55)	84
	5T4-specific Fab fused to the SEA/E-120 superantigen (Naptumomab estafenatox (nap))	None	Not restricted	IFN-α	II/III	metastatic clear cell or papillary RCC	Nap + IFN-α (N = 253) or IFN-α (N = 260)	Not applicable	Primary endpoint OS was not increased; Median OS 17.1 (Nap + IFN) vs 17.5 mo (IFN); HR 1.08 (P = 0.56)	105
MUC1	2 HLA class I peptides loaded on DC	Pan-DR class II peptide (PADRE)	HLA-A*0201	Low-dose IL-2	I/II	ccRCC with MUC1 expression	N = 20	Peptide reactive CTL responses in 12/20 (60%) patients	1 CR, 2 PR (15%)	85
	Recombinant MVA expressing MUC1 and IL-2 (TG4010)	None	Not restricted	None, IL-2, or IFN-α	I/II	mRCC	N = 37	6/23 (26%) CD8+ responses; 5/28 (18%) CD4+ responses	No objective responses	86
WT-1	1 HLA class I synthetic peptide	Montanide ISA-51	HLA-A*2402	IL2 or IL2 and IFN-α	I	RCC	N = 3	Peptide reactive CTL responses in 2/2 evaluated patients	No objective responses	87
	Autologous DCs loaded with 1 HLA class I synthetic peptide per patient; matched to HLA expression	OK-432	HLA-A*02:01, *02:06 or *24:02	None	I/II	Treatment refractory ccRCC or BC with WT1 expression	N = 5 RCC (plus 5 bladder cancer)	Peptide reactive CTL responses in 5/5 patients by tetramer staining, ELISPOT or cytoplasmic IFN-γ assays	No objective responses	88

Abbreviations: PR: partial responses, SD: stable disease, CR: complete response, PD: progressive disease, NED: no evidence of disease; OS: overall survival, SAE:serious adverse events, PADRE: pan-HLA-class II binding peptide

Table 3. Clinical testing of multiple antigen vaccines for advanced RCC

Immune Targets	Antigen Formulation	Adjuvant	HLA restriction	Combination therapy	Phase	Enrollment		Cellular Immune Response	Clinical Outcome	Reference
						Key Criteria	N
personalized peptide vaccine^1	4 HLA class I synthetic peptides per patient from a pool of 25 HLA-A24 and 23 HLA-A2 peptides	Montanide ISA-51VG	HLA-A*02 or *24	None	I	Cytokine-refractory mRCC	N = 10	Peptide reactive CTL responses in 2/10 (20%) patients	No objective responses	89
telomerase and survivin	8 telomerase + 11 survivin synthetic peptides (or tumor lysate for non HLA-A2 cohort) loaded on DC	Pan-DR class II peptide (PADRE)	HLA-A*02+ for peptide vaccine	Low-dose IL-2	I/II	Progressive mRCC	A2^+ peptide pulsed DC (n = 13) or A2- tumor lysate pulsed DC (n = 14)	CTL against 1 or more survivin/telomerase peptides in 6/6 A2^+ patients	No objective responses	90
multiple tumor- associated peptides^Citation2	9 HLA class I synthetic peptides plus 1 class II peptide. (Phase I included class I marker HBV peptide)	GM-CSF	HLA-A*02	None	I	mRCC	N = 28	20/27 (74%) patients developed CTL response to one or more peptide; 8/27 (22%) responded to more than one peptide; 14/27 (52%) responded to HBV	1 PR (4%)	91
	9 HLA class I synthetic peptides plus 1 class II peptide (IMA901)	GM-CSF	HLA-A*02	None or low-dose cyclophosphamide (Cy)	II	TKI or cytokine-refractory metastatic RCC	Cy + IMA901 (n = 33) or IMA901 (n = 35)	64% patients developed CTL response for one or more peptide; 26% patients responded to more than one antigen	1 CR, 2 PR (4%); investigator assessed	91
				Sunitinib	III (IMPRINT)	metastatic ccRCC; no prior systemic therapy	Sunitinib + IMA901 (n = 204) or sunitinib monotherapy (n = 135)	3-fold decrease of tumor-peptide specific CD8+ response compared with the phase I/II	Primary endpoint OS was not increased; Median OS 33.2 mo (IMA901+ Su) versus NR (Su); HR 1.34 (P = 0.087)	92
autologous tumor RNA-endcoded antigens	Autologous DCs co-electroporatedwith amplified tumor RNA and syntheticCD40L RNA (AGS-003, Rocapuldencel-T)	syntheticCD40L RNA	Not restricted	Sunitinib	II	metastatic ccRCC; no prior systemic therapy	N = 21	10 of 14 (71%) patients displayed an increasein CD28^+/CD45RA^− CTLsover baseline	9/21 PR (43%)	93
			Not restricted	Sunitinib	III (ADAPT)	metastatic ccRCC; no prior systemic therapy	AGS-003+ sunitinib (n = 307) or sunitinib (n = 155)	Immune responders (increased CD28+/CD45RA- CTL) after Rocapuldencel-T administration was 72% to 82%	Primary endpoint OS was not increased; Median OS 27.7 mo (AGS003+ Su) versus 32.4 (Su); HR 1.10	94

¹Antigen targets: SART1, SART2, SART3, MRP3, EZH2, HER2/neu, PTHrP, PSA and PAP, CEA, UBE and Lck. ²Antigen targets: (class I) PLIN2, APOL1, CCND1, GUCY1A3, PRUNE2, MET, MUC1, RGS5; (class II) MMP7. Abbreviations: PR: partial responses, SD: stable disease, CR: complete response, PD: progressive disease, NED: no evidence of disease; OS: overall survival, SAE: serious adverse events, PADRE: pan-HLA-class II binding peptide

Table 4. Active trials with engineered T-cell therapy enrolling metastatic RCC patients

Antigen target	Phase	Specific RCC Setting	Engineered T-cells	Combination	Clinicaltrials.gov identifier
CD70	I/II	CD70+ ccRCC	autologous CAR-T	fludarabine, cyclophosphamide, high-dose IL-2	NCT02830724
CD70	I	ccRCC	allogeneic CAR-T-cells with CRISPR-Cas9 targeting of MHC I and endogenous TCR (CTX130)	lymphodepleting chemotherapy	NCT04438083
c-MET	I/II	c-MET+ RCC	autologous CAR-T	fludarabine, cyclophosphamide	NCT03638206
personalized neoantigen	I	individual neoantigen target(s)	autologous TCR-transduced	fludarabine, cyclophosphamide, high-dose IL-2	NCT04596033
hERV-E	I	ccRCC, HLA-A*11:01+	autologous TCR-transduced CD8+/CD34+	fludarabine, cyclophosphamide, moderate-dose IL-2	NCT03354390

Abbreviations: RCC – renal cell carcinoma; IL-2 – interleukin 2; CAR – chimeric antigen receptor; HLA – human leulocyte antigen; TCR – T-cell receptor

Brandle D, Brasseur F, Weynants P, Boon T, Van den Eynde B. A mutated hla-a2 molecule recognized by autologous cytotoxic t lymphocytes on a human renal cell carcinoma. J Exp Med. 1996;183(6):2501–08. doi:10.1084/jem.183.6.2501.

 PubMed Web of Science ®Google Scholar

Gaudin C, Kremer F, Angevin E, Scott V, Triebel F. A hsp70–2 mutation recognized by ctl on a human renal cell carcinoma. J Immunol. 1999;162:1730–38.

 PubMed Web of Science ®Google Scholar

Gaugler B, Brouwenstijn N, Vantomme V, Szikora JP, Van der Spek CW, Patard JJ, Boon T, Schrier P, Van den Eynde BJ. A new gene coding for an antigen recognized by autologous cytolytic t lymphocytes on a human renal carcinoma. Immunogenetics. 1996;44(5):323–30. doi:10.1007/BF02602776.

 PubMed Web of Science ®Google Scholar

Morel S, Levy F, Burlet-Schiltz O, Brasseur F, Probst-Kepper M, Peitrequin AL, Monsarrat B, Van Velthoven R, Cerottini JC, Boon T, et al. Processing of some antigens by the standard proteasome but not by the immunoproteasome results in poor presentation by dendritic cells. Immunity. 2000;12(1):107–17. doi:10.1016/S1074-7613(00)80163-6.

 PubMed Web of Science ®Google Scholar

Probst-Kepper M, Stroobant V, Kridel R, Gaugler B, Landry C, Brasseur F, Cosyns JP, Weynand B, Boon T, Van den Eynde BJ. An alternative open reading frame of the human macrophage colony-stimulating factor gene is independently translated and codes for an antigenic peptide of 14 amino acids recognized by tumor-infiltrating cd8 t lymphocytes. J Exp Med. 2001;193(10):1189–98. doi:10.1084/jem.193.10.1189.

 PubMed Web of Science ®Google Scholar

Ronsin C, Chung-Scott V, Poullion I, Aknouche N, Gaudin C, Triebel F. A non-aug-defined alternative open reading frame of the intestinal carboxyl esterase mrna generates an epitope recognized by renal cell carcinoma-reactive tumor-infiltrating lymphocytes in situ. J Immunol. 1999;163:483–90.

 PubMed Web of Science ®Google Scholar

Van Den Eynde BJ, Gaugler B, Probst-Kepper M, Michaux L, Devuyst O, Lorge F, Weynants P, Boon T. A new antigen recognized by cytolytic t lymphocytes on a human kidney tumor results from reverse strand transcription. J Exp Med. 1999;190(12):1793–800. doi:10.1084/jem.190.12.1793.

 PubMed Web of Science ®Google Scholar

Hanada K, Yewdell JW, Yang JC. Immune recognition of a human renal cancer antigen through post-translational protein splicing. Nature. 2004;427(6971):252–56. doi:10.1038/nature02240.

 PubMed Web of Science ®Google Scholar

Yarchoan M, Hopkins A, Jaffee EM. Tumor mutational burden and response rate to pd-1 inhibition. N Engl J Med. 2017;377(25):2500–01. doi:10.1056/NEJMc1713444.

 PubMed Web of Science ®Google Scholar

Uemura H, Fujimoto K, Tanaka M, Yoshikawa M, Hirao Y, Uejima S, Yoshikawa K, Itoh K. A phase i trial of vaccination of ca9-derived peptides for hla-a24-positive patients with cytokine-refractory metastatic renal cell carcinoma. Clin Cancer Res. 2006;12(6):1768–75. doi:10.1158/1078-0432.CCR-05-2253.

 PubMed Web of Science ®Google Scholar

Bleumer I, Tiemessen DM, Oosterwijk-Wakka JC, Voller MC, De Weijer K, Mulders PF, Oosterwijk E. Preliminary analysis of patients with progressive renal cell carcinoma vaccinated with ca9-peptide-pulsed mature dendritic cells. J Immunother. 2007;30(1):116–22. doi:10.1097/01.cji.0000211318.22902.ec.

 PubMed Web of Science ®Google Scholar

Lamers CH, Sleijfer S, van Steenbergen S, van Elzakker P, van Krimpen B, Groot C, Vulto A, den Bakker M, Oosterwijk E, Debets R, et al. Treatment of metastatic renal cell carcinoma with caix car-engineered t cells: clinical evaluation and management of on-target toxicity. Mol Ther. 2013;21(4):904–12. doi:10.1038/mt.2013.17.

 PubMed Web of Science ®Google Scholar

Yoshimura K, Minami T, Nozawa M, Uemura H. Phase i clinical trial of human vascular endothelial growth factor receptor 1 peptide vaccines for patients with metastatic renal cell carcinoma. Br J Cancer. 2013;108(6):1260–66. doi:10.1038/bjc.2013.90.

 PubMed Web of Science ®Google Scholar

Obara W, Karashima T, Takeda K, Kato R, Kato Y, Kanehira M, Takata R, Inoue K, Katagiri T, Shuin T, et al. Effective induction of cytotoxic t cells recognizing an epitope peptide derived from hypoxia-inducible protein 2 (hig2) in patients with metastatic renal cell carcinoma. Cancer Immunol Immunother. 2017;66(1):17–24. doi:10.1007/s00262-016-1915-5.

 PubMed Web of Science ®Google Scholar

Rahma OE, Ashtar E, Ibrahim R, Toubaji A, Gause B, Herrin VE, Linehan WM, Steinberg SM, Grollman F, Grimes G, et al. A pilot clinical trial testing mutant von hippel-lindau peptide as a novel immune therapy in metastatic renal cell carcinoma. J Transl Med. 2010;8(1):8. doi:10.1186/1479-5876-8-8.

 PubMed Web of Science ®Google Scholar

Amato RJ, Shingler W, Naylor S, Jac J, Willis J, Saxena S, Hernandez-McClain J, Harrop R. Vaccination of renal cell cancer patients with modified vaccinia ankara delivering tumor antigen 5t4 (trovax) administered with interleukin 2: A phase ii trial. Clin Cancer Res. 2008;14(22):7504–10. doi:10.1158/1078-0432.CCR-08-0668.

 PubMed Web of Science ®Google Scholar

Kaufman HL, Taback B, Sherman W, Kim DW, Shingler WH, Moroziewicz D, DeRaffele G, Mitcham J, Carroll MW, Harrop R, et al. Phase ii trial of modified vaccinia ankara (mva) virus expressing 5t4 and high dose interleukin-2 (il-2) in patients with metastatic renal cell carcinoma. J Transl Med. 2009;7(2). doi:10.1186/1479-5876-7-2.

 PubMed Web of Science ®Google Scholar

Hawkins RE, Macdermott C, Shablak A, Hamer C, Thistlethwaite F, Drury NL, Chikoti P, Shingler W, Naylor S, Harrop R. Vaccination of patients with metastatic renal cancer with modified vaccinia ankara encoding the tumor antigen 5t4 (trovax) given alongside interferon-alpha. J Immunother. 2009;32(4):424–29. doi:10.1097/CJI.0b013e31819d297e.

 PubMed Web of Science ®Google Scholar

Amato RJ, Shingler W, Goonewardena M, de Belin J, Naylor S, Jac J, Willis J, Saxena S, Hernandez-McClain J, Harrop R. Vaccination of renal cell cancer patients with modified vaccinia ankara delivering the tumor antigen 5t4 (trovax) alone or administered in combination with interferon-alpha (ifn-alpha): A phase 2 trial. J Immunother. 2009;32(7):765–72. doi:10.1097/CJI.0b013e3181ace876.

 PubMed Web of Science ®Google Scholar

Amato RJ, Hawkins RE, Kaufman HL, Thompson JA, Tomczak P, Szczylik C, McDonald M, Eastty S, Shingler WH, de Belin J, et al. Vaccination of metastatic renal cancer patients with mva-5t4: A randomized, double-blind, placebo-controlled phase iii study. Clin Cancer Res. 2010;16(22):5539–47. doi:10.1158/1078-0432.CCR-10-2082.

 PubMed Web of Science ®Google Scholar

Stern PL, Harrop R. 5t4 oncofoetal antigen: an attractive target for immune intervention in cancer. Cancer Immunol Immunother. 2017;66(4):415–26. doi:10.1007/s00262-016-1917-3.

 PubMed Web of Science ®Google Scholar

Wierecky J, Muller MR, Wirths S, Halder-Oehler E, Dorfel D, Schmidt SM, Hantschel M, Brugger W, Schroder S, Horger MS, et al. Immunologic and clinical responses after vaccinations with peptide-pulsed dendritic cells in metastatic renal cancer patients. Cancer Res. 2006;66(11):5910–18. doi:10.1158/0008-5472.CAN-05-3905.

 PubMed Web of Science ®Google Scholar

Oudard S, Rixe O, Beuselinck B, Linassier C, Banu E, Machiels JP, Baudard M, Ringeisen F, Velu T, Lefrere-Belda MA, et al. A phase ii study of the cancer vaccine tg4010 alone and in combination with cytokines in patients with metastatic renal clear-cell carcinoma: clinical and immunological findings. Cancer Immunol Immunother. 2011;60(2):261–71. doi:10.1007/s00262-010-0935-9.

 PubMed Web of Science ®Google Scholar

Iiyama T, Udaka K, Takeda S, Takeuchi T, Adachi YC, Ohtsuki Y, Tsuboi A, Nakatsuka S, Elisseeva OA, Oji Y, et al. Wt1 (wilms’ tumor 1) peptide immunotherapy for renal cell carcinoma. Microbiol Immunol. 2007;51(5):519–30. doi:10.1111/j.1348-0421.2007.tb03940.x.

 PubMed Web of Science ®Google Scholar

Ogasawara M, Miyashita M, Ota S. Vaccination of urological cancer patients with wt1 peptide-pulsed dendritic cells in combination with molecular targeted therapy or conventional chemotherapy induces immunological and clinical responses. Ther Apher Dial. 2018;22(3):266–77. doi:10.1111/1744-9987.12694.

 PubMed Web of Science ®Google Scholar

Suekane S, Nishitani M, Noguchi M, Komohara Y, Kokubu T, Naitoh M, Honma S, Yamada A, Itoh K, Matsuoka K, et al. Phase i trial of personalized peptide vaccination for cytokine-refractory metastatic renal cell carcinoma patients. Cancer Sci. 2007;98(12):1965–68. doi:10.1111/j.1349-7006.2007.00631.x.

 PubMed Web of Science ®Google Scholar

Berntsen A, Trepiakas R, Wenandy L, Geertsen PF, Thor Straten P, Andersen MH, Pedersen AE, Claesson MH, Lorentzen T, Johansen JS, et al. Therapeutic dendritic cell vaccination of patients with metastatic renal cell carcinoma: a clinical phase 1/2 trial. J Immunother. 2008;31(8):771–80. doi:10.1097/CJI.0b013e3181833818.

 PubMed Web of Science ®Google Scholar

Motzer RJ, Mazumdar M, Bacik J, Berg W, Amsterdam A, Ferrara J. Survival and prognostic stratification of 670 patients with advanced renal cell carcinoma. J Clin Oncol. 1999;17(8):2530–40. doi:10.1200/JCO.1999.17.8.2530.

 PubMed Web of Science ®Google Scholar

Walter S, Weinschenk T, Stenzl A, Zdrojowy R, Pluzanska A, Szczylik C, Staehler M, Brugger W, Dietrich PY, Mendrzyk R, et al. Multipeptide immune response to cancer vaccine ima901 after single-dose cyclophosphamide associates with longer patient survival. Nat Med. 2012;18(8):1254–61. doi:10.1038/nm.2883.

 PubMed Web of Science ®Google Scholar

Rini BI, Stenzl A, Zdrojowy R, Kogan M, Shkolnik M, Oudard S, Weikert S, Bracarda S, Crabb SJ, Bedke J, et al. Ima901, a multipeptide cancer vaccine, plus sunitinib versus sunitinib alone, as first-line therapy for advanced or metastatic renal cell carcinoma (imprint): a multicentre, open-label, randomised, controlled, phase 3 trial. Lancet Oncol. 2016;17(11):1599–611. doi:10.1016/S1470-2045(16)30408-9.

 PubMed Web of Science ®Google Scholar

Amin A, Dudek AZ, Logan TF, Lance RS, Holzbeierlein JM, Knox JJ, Master VA, Pal SK, Miller WH Jr., Karsh LI, et al. Survival with ags-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (rcc): phase 2 study results. J Immunother Cancer. 2015;3(14). doi:10.1186/s40425-015-0055-3.

 PubMed Web of Science ®Google Scholar

Figlin RA, Tannir NM, Uzzo RG, Tykodi SS, Chen DYT, Master V, Kapoor A, Vaena D, Lowrance WT, Bratslavsky G, et al. Results of the adapt phase 3 study of rocapuldencel-t in combination with sunitinib as first-line therapy in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2020;26:2327–36. doi:10.1158/1078-0432.CCR-19-2427.

 PubMed Web of Science ®Google Scholar