Table 1 IL-7-based viral vectors in cancer therapy.
From: Promoting the therapeutic potential of interleukin-7 (IL-7) by expression in viral vectors
Name | Description | Tested model(s) | Treatment route | Major outcomes | Refs. |
|---|---|---|---|---|---|
Ad5/3-E2F-d24-hIL7 (TILT-517) | Oncolytic adenovirus (oAd) coding human IL-7 | HapT1 pancreatic cancer | Intratumoral | ○ Significantly controlled tumor burden compared to control oAd (Ad5/3-E2F-d24) ○ Increased T cell activation and intratumoral infiltration of CD8+ T cells and Mac-2+ monocytes/macrophages ○ Elevated levels of CD4+, CD8+ T, and MHCII+ cells in the blood | [27] |
Patient-derived xenograft model of ovarian cancer | Intratumoral | ○ Significantly inhibited tumor growth compared to a non-IL7-expressing oAd in mice receiving an intraperitoneal infusion of peripheral blood mononuclear cells | [27] | ||
Ex vivo patient-derived ovarian cancer samples | Direct inoculation | ○ Induced a higher pro-inflammatory/anti-inflammatory cytokine ratio than Ad5/3-E2F-d24 or mock ○ Substantial increase in ex vivo recruitment of cytotoxic CD4+ and CD8+ T cells in TILT-517-treated samples | [27] | ||
LX/IL-7 | A non-lytic Newcastle disease virus (NDV) expressing IL-7 | B16-F10; EL-4 | Subcutaneous injections with B16-LX/IL-7 or EL4-LX/IL7 [B16-LX/IL-7 or EL4-LX/IL7: LX/IL-7 loaded in irradiated B16-F10 murine melanoma (i.e., B16-LX/IL-7) or EL-4 murine lymphoma cells (i.e., EL4-LX/IL7)] | Prophylactic: ○ B16-LX/IL-7 or EL4-LX/IL7 significantly inhibited homologous but not heterologous tumor growth compared to vaccination with irradiated B16-F10 cells loaded with LX strain expressing a red fluorescent protein (RFP) ○ Enhanced tumor-specific IFN-γ response Therapeutic: ○ B16-LX/IL-7 or EL4-LX/IL7 significantly inhibited homologous tumor growth (vs. controls) ○ Significantly increased infiltration of both CD4+ and CD8+ T cells into tumors (vs. controls), with an enhanced tumor-specific IFN-γ response ○ CD8+ T cell-dependent efficacy | [28] |
oAd-IL7 | oAd-expressing human IL-7 | Orthotopic glioblastoma xenograft | Intratumoral oAd-IL7 plus intravenous B7-H3-expressing CAR-T cells | ○ The combination resulted in a significant proportion of long-term survivors (i.e., 80%) ○ Increased tumoral infiltration of B7H3-CAR-T cells and significantly higher levels of Ki67 in the infiltrated CAR-T cells ○ Increased expression of T-cell exhaustion markers, such as LAG-3 and PD-1 | [29] |
hIL7-VV, mIL12-VV | Oncolytic vaccinia virus expressing human IL-7 or murine IL-12 | LLC lung carcinoma | Intratumoral | ○ IL-7 expression (hIL7-VV) had no significant antitumor effects ○ IL-12 expression (mIL12-VV) inhibited tumor growth, achieving a complete response in 1/7 (14.3%) animals ○ The combination of hIL7-VV plus mIL12-VV (versus monotherapies) resulted in 57.1% (4/7) complete response rate, which was associated with a significant intratumoral infiltration of CD4+ T and NKT cells | [30] |
hIL7/mIL12-VV | Oncolytic vaccinia virus co-expressing human IL-7 plus murine IL-12 | B16-F10; CT26.WT | Intratumoral | ○ Viral co-expression of IL-7 plus IL-12 (hIL7/mIL12-VV), resulted in a complete response in 75% (6/8) animals compared to 25% (2/8) in the cont-VV control group in B16-F10 model ○ CD8+ (not CD4+) T cell-dependent efficacy in the CT26.WT model | [30] |
Bilateral CT26.WT | Intratumoral | ○ hIL7/mIL12-VV injection into one tumor resulted in 100% (6/6) eradication of injected tumors and 50% (3/6) of non-injected contralateral tumors ○ Viral DNA was detected only in injected tumors ○ Significantly increased intratumoral infiltration of conventional T (CD4+FoxP3-), CD8+ T, NKT, NK, and regulatory T cells (CD4+FoxP3+) in both injected and distant tumors ○ Generated tumor antigen-specific (gp70+CD8+) T cells in both injected and distant tumors ○ Development of tumor-specific immune memory ○ Synergizes with anti-PD-1 or anti-CTLA-4 and eradicated 60% and 40% of non-injected tumors | (30) | ||
Bilateral LLC | Intratumoral | ○ hIL7/mIL12-VV reduced tumor growth by 43.1% in both injected and non-injected tumors ○ Viral DNA was present in both tumors | [30] | ||
hIL7/hIL12-VV | Oncolytic vaccinia virus co-expressing human IL-7 and human IL-12 | HCT 116; U87; Detroit 562 | Intratumoral | ○ hIL7/hIL12-VV led to significant tumor regression compared to mock treatment in all three subcutaneous tumor models in nude mice | [30] |
NCI-H1373 | Intratumoral | ○ hIL7/hIL12-VV was significantly more effective than cont-VV in reducing tumor burden in humanized mice bearing subcutaneous NCI-H1373 tumors ○ Enhanced intratumoral infiltration of CD4+, CD8+ T, NKT, and NK cells compared to cont-VV or PBS | [30] | ||
SINV-IL7 or SINV-IL12 | Sindbis virus (SINV) expressing IL-7 or IL-12 | U-87MG GBM | Intratumoral | ○ SINV-IL7 or SINV-IL12 demonstrated superior efficacy compared to control SINV in subcutaneously implanted U-87MG GBM model | [61] |
SINV-IL7/IL12 | A SINV co-expressing IL-7 plus IL-12 | Intracranial U-87MG GBM | Intratumoral | ○ SINV-IL7/IL12 enhanced tumor suppression compared to SINV-IL7 or SINV-IL12, with SINV-IL7/IL12 achieved 80% long-term survivors | [61] |
LX/IL(15 + 7) | A non-lytic NDV LX strain co-expressing IL-7 plus IL-15 | B16-F10; EL-4 | Subcutaneous injections with B16-LX/IL(15 + 7) [B16-LX/IL(15 + 7) is described as irradiated B16-F10 cells loaded with LX/IL(15 + 7) virus] | Prophylactic: ○ LX/IL(15 + 7)-modified B16-F10 cells (B16-LX/IL(15 + 7)) or control LX/RFP-modified B16-F10 cells (i.e., B16-LX/RFP) significantly inhibited B16-F10 tumor growth compared to irradiated B16-F10 cells without virus loading ○ The B16-LX/IL(15 + 7) vaccine demonstrated a significantly superior prophylactic antitumor effect than the control B16-LX/RFP vaccine ○ Both B16-LX/IL(15 + 7) and B16-LX/RFP vaccines similarly enhanced infiltration of CD4+ and CD8+ T cells into tumors compared to irradiated B16-F10 cells Therapeutic: ○ The therapeutic B16-LX/IL(15 + 7) vaccine significantly inhibited B16-F10 tumor growth compared to the B16-LX/RFP vaccine ○ The antitumor effect of the B16-LX/IL(15 + 7) vaccine was tumor-specific ○ B16-LX/IL(15 + 7) vaccine significantly increased intratumoral infiltration of CD3+, CD4+, and CD8+ T cells (vs. B16-LX/RFP), and the vaccine efficacy was CD8+ T cell-dependent | [31] |
Ad.IL-7/B7.1 | A replication-defective adenovirus co-expressing IL-7 plus B7.1 | TS/A adenocarcinoma | Intratumoral | ○ Ad.IL-7/B7.1 treatment led to 70% (7/10) tumor-free long-term survivors compared to no survivors in the Ad.βgal group in transplanted TS/A model ○ Ad.IL-7/B7.1 treatment enhanced the infiltration of CD4+ and CD8+ T cells into transplanted TS/A tumors compared to the control, and its efficacy was abrogated in the absence of T cells ○ Ad.IL-7/B7.1 treatment provided 100% immune memory protection | [32] |
oHSV2-IL7×CCL19 | A type 2 oHSV co-expressing IL-7 plus CCL19 | CT26 | Intratumoral | ○ The oHSV2-IL7×CCL19 treatment showed better, but not statistically significant, efficacy than the other control viruses expressing IL-12, anti-PD-1, or IL-15 | [82] |
