Table 1.
Recent examples of neoantigen vaccine delivery.
| Status | Indication | Antigen | Adjuvant | Route | T cell responses | ||
|---|---|---|---|---|---|---|---|
| CD4+ | CD8+ | Reference | |||||
| 1. Direct injection of unformulated neoantigen vaccines | |||||||
| Phase I | Melanoma (stage III and IV) |
mRNA | None | i.n. | 0.1–2.0%a | 0.02–0.55%a 0.03–1.9%b |
(16) |
| Phase I | Melanoma (stage IIIB/C and IVM1a/b) |
SLP | Poly-ICLC | s.c. | 0.03–0.06%a 0.001–0.05%b |
0.2–1.2%c | (17) |
| Preclinical study | MC-38 colon cancer | SLP | CD40 antibody and poly (I:C) | i.p. | NM | 0.18–1.4%a 0.48–1.33%b |
(19) |
| Preclinical study | B16F10 melanoma | SLP | Poly(I:C) | s.c. | 1.54%c | 3.61%c | (20) |
| Preclinical study | d42m1-T3 sarcoma | SLP | Poly(I:C) | s.c. | NM | 2.8–17.5%b | (21) |
| Preclinical study | A2.DR1 sarcoma | SLP | CFA, montanide-ISA51, and imiquimod | s.c. | 1.91%b | NM | (22) |
| Preclinical study | B16F10 melanoma | SLP | Poly(I:C) | s.c. | NM | NM | (23) |
| 2. Ex vivo-pulsed dendritic cell (DC) vaccine | |||||||
| Phase I | Melanoma (stage III) | Ex vivo SLP pulsed DCs | Poly(I:C), R848 | i.v. | NM | 0.06–0.9%a | (15) |
| 3. Biomaterials-assisted neoantigen vaccines | |||||||
| Preclinical study | B16F10 melanoma, 4T1 breast cancer, and CT26 colon cancer | mRNA-lipoplex | None | i.v. | 1.36%c | 1.67%c | (20) |
| Preclinical and phase I study | CT26 colon cancer, TC-1, and melanoma | mRNA-lipoplex | None | i.v. | NM | 30–60%a, 0.62%a |
(24) |
| Preclinical study | MC-38 colon cancer and E6/7-TC-1 lung cancer | SLP/PC7A nanoparticles | None | s.c. | NM | NM | (25) |
| Preclinical study | MC-38 colon cancer and B16F10 melanoma | SLP/nanodiscs | CpG | s.c. | ~14.0%c | ~30%a | (26) |
| Preclinical study | B16F10 melanoma | Endogenous neoantigen-containing proteins | None | s.c. | 1.0–3.0%c | 1.5–12%c | (27) |
| Preclinical study | E7-TC-1 lung cancer, B16F10 melanoma, and CT26 colon cancer | SLP/mesoporous silica microrod with PEI | CpG, PEI | s.c. | ~0.6%c | ~2.0%a 1.5%c |
(28) |
| Preclinical study | MC-38 colon cancer | SLP/DNA-RNA nanocapsule | CpG | s.c. | NM | 9.5%a | (29) |
aPercentage of neoantigen-specific CD4+ (or CD8+) T cells among total CD4+ (or CD8+) T cells in peripheral blood or spleen detected by multimer staining or the Enzyme-Linked ImmunoSpot (ELISPOT) assay.
bPercentage of neoantigen-specific CD4+ (or CD8+) T cells among total CD4+ (or CD8+) T cells in tumor detected by multimer staining.
cPercentage of neoantigen-specific CD4+ (or CD8+) T cells among total CD4+ (or CD8+) T cells in peripheral blood or spleen detected by intracellular interferon-γ (IFN-γ) staining.
i.n., intranodal injection; s.c., subcutaneous injection; i.v., intravenous injection; i.p., intraperitoneal injection; NM, not measured; poly-ICLC, polyriboinosinic-polyribocytidylic acid-polylysine carboxymethylcellulose; poly(I:C), polyinosinic:polycytidylic acid; SLP, synthetic long peptide; CFA, complete Freund’s adjuvant; CpG, unmethylated cytosine-phosphate-guanine oligodeoxynucleotides; PEI, polyethyleneimine.