Preclinical support for tumor protein D52 as a cancer vaccine antigen

Figures & data

Figure 1. Tumor protein D52 TAA characteristics. Illustrated are the three characteristics of TPD52 defining it as a universal tumor-associated antigen (TAA). Shown are natural cellular expression characteristics (red), oncogenic characteristics (yellow) and immunogenic characteristics as elicited by vaccination with TPD52 (blue). Figure was created using BioRender.

Table 1. Overview of preclinical TPD52 vaccine studies.

Mouse Strain/Tumor Model	Vaccine, Adjuvant & Route	Tumor Protective Response	CD8 T Cell Profile/ MHC-I restriction	Autoimmunity
Balb/c/Sarcomas	S1) mD52 protein/ODN-alum i.m. (ref. 74)	40–50% s.c. primary tumor 100% s.c. secondary tumor 100% spontaneous lung mets 70% s.c. primary tumor	CD8 IFN-γ CTLs/H-2K^d CD8 IL-10 T cells/H-2K^d	None
	S2) mD52 protein/ODN-IFA s.c. + CD4 CD25 Treg depletion (ref. 76)	100% s.c. secondary tumor 100% spontaneous lung mets	CD8 IFN-γ CTLs/H-2K^d CD8 IL-10 T cells/H-2K^d	None
C57BL/6/Prostate cancer	S1) mD52 DNA/rGM-CSF PBS s.c. (ref. 75)	70% primary tumor 100% secondary tumor	CD8 IFN-γ CTLs/H-2Kb CD8 IL-10 T cells/H-2K^b	None
	S2) hD52 DNA/PBS i.m.	70% primary tumor 100% secondary tumor	CD8 IFN-γ CTLs/H-2K^b CD8 IL-10 T cells/H-2Kb	None
	mD52 DNA/PBS i.m.	50% primary tumor 100% secondary tumor	CD8 IFN-γ CTLs/H-2K^b CD8 IL-10 T cells/H-2K^b (CD8 T cells FOXP3 negative)	None
	mD52 DNA/ PBS i.m. + CD4 CD25 Treg depletion(ref. 77)	50% primary tumor 100% secondary tumor	CD8 IFN-γ CTLs/ H-2K^b CD8 IL-10 T cells/ H-2K^b (CD8 T cells FOXP3negative)	None
	S3) hD52 DNA/ PBS i.m. prime-mD52 protein/ODN-IFA s.c. boost	80% primary tumor ~100% secondary tumor	CD8 IFN-γ CTLs/ H-2K^b CD8 IL-10 T cells/ H-2K^b (CD4 and CD8 T cells played critical role)	None
B6 IL-10 KO/Prostate cancer	S4) mD52 DNA/PBS i.m. (ref. 79)	increased for primary tumor 100% secondary tumor	CD8 IFN-γ CTLs/H-2K^b CD8 IL-10 T cells/H-2K^b	None

Figure 2. Percent of tumor free animals following heterologous prime-boost immunization: male C57Black/6 mice were vaccinated with human TPD52 (hD52-DNA) i.M. For three injections ending with recombinant mouse TPD52 protein (mD52-protein) + ODN s.C. Tumor challenge was administered 14 days later with mD52+ TRAMP-C2 cells. Mice immunized with control vaccines developed tumors (control). A role for CD4 and CD8 T cells was assessed in response to vaccination and tumor challenge by in vivo depletion of the specific T cell subsets: (a) CD4 or (b) CD8 compared to vaccinated and mock depleted mice.