Vascular Endothelial Growth Factor-Trap Overcomes Defects in Dendritic Cell Differentiation but Does Not Improve Antigen-Specific Immune Responses

Abstract

Purpose: Induction of antitumor immune responses requires adequate function of dendritic cells.

Rationally Combining Anti-VEGF Therapy with Checkpoint Inhibitors in Hepatocellular Carcinoma

“…Interestingly, VEGFR2 is only expressed by pDCs resident in tissues but not in peripheral blood or bone marrow pDCs, suggesting that VEGFR2 may be a maturation marker for these cells. However, despite the accumulating evidence that VEGF could inhibiting the maturation and activity of DC populations, blockade of VEGF signaling alone may not be sufficient to promote DC maturation [63], likely due to other immunosuppressive cues.…”

Targeted Delivery of an Antibody–Mutant Human Endostatin Fusion Protein Results in Enhanced Antitumor Efficacy

“…There are several examples of fusions in approved clinical use in which antigenicity has not been a major problem including anti-TNFR-fusions (33,34), DAB 389 IL-2 (35), and VEGFR-fusion (VEGF-Trap in patients with solid tumors and non-Hodgkin's lymphomas; ref. 36). Therefore, the effects of antigenicity on efficacy cannot be predicted a priori from mouse models.…”

“…Because the overall response rates of HER2þ breast cancers to trastuzumab remain relatively low (15%-34%; refs. [36][37][38][39], this approach holds promise for increasing both response rate and duration relative to trastuzumab, and may expand the spectrum of antitumor activity of trastuzumab given alone or in combination with other antitumor strategies such as other cytotoxic agents (carboplatin, docetaxel; refs. [40][41][42][43], and/or antiangiogenic drugs (e.g., bevacizumab; anti-VEGF antibody, thrombospondin-1; refs.…”

Advances in cancer immunology and cancer immunotherapeutics

“…Some of the suggested approaches are to promote differentiation of the MDSCs into mature myeloid cells with no suppressive effects (Vitamin D3 and all-trans retinoic acids), inhibit MDSCs expansion (KIT-specific Ab, VEGF-trap) or inhibit MDSCs functions (cyclooxygenase-2 inhibitors). [50][51][52][53][54] Polarization to TH2 response has been associated with poor prognosis and promoted in TME. Recently, matrix metalloproteinase-2 (MMP-2) produced by the tumor cells has been linked to promoting TH2 response by acting directly as an antigen, increased OX40L expression and DCs receptor alteration.…”