The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy
Abstract
:Simple Summary
Abstract
1. Introduction
2. Expression Pattern of Flt3 and Flt3L
3. Flt3 Signaling in Response to Its Ligand
4. Expansion of DCs with Flt3L
5. Preclinical Studies Involving Flt3L
6. Flt3L in the Clinic
7. Conclusions and Future Perspective
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Identifier | Title | Indication | Therapeutic Strategy | Accrual | Clinical Trial Phase |
---|---|---|---|---|---|
Status: Completed | |||||
NCT00006223 | Flt3L in Treating Patients With Acute Myeloid Leukemia | Acute myeloid leukemia in remission | S.c. recombinant FLT3L vs. observation alone | 139 * | III |
NCT00003431 | Flt3L in Treating Patients With Metastatic Colorectal Cancer | Metastatic colorectal cancer | S.c. recombinant FLT3L before resection of hepatic metastases | 12 * | I |
NCT00019396 | Flt3L With or Without Vaccine Therapy in Treating Patients With Metastatic Melanoma or Renal Cell Cancer | Stage IV melanoma, stage IV renal cell cancer, recurrent renal cell cancer and recurrent melanoma | S.c. recombinant FLT3L alone or with melanoma-associated peptides | 54–96 * | II |
NCT00020540 | Biological Therapy in Treating Patients With Metastatic Melanoma or Metastatic Kidney Cancer | Metastatic skin melanoma and metastatic kidney cancer | S.c. recombinant FLT3L with s.c. recombinant CD40L | 5 * | I |
NCT01465139 | A Study to Evaluate CDX-301 (rhuFlt3L) in Healthy Volunteers | Healthy volunteers | Escalating doses of s.c. recombinant FLT3L (CDX-301) | 30 | I |
NCT01484470 | Umbilical Cord Transplantation for the Elderly Population | Multiple hematologic malignancies | Biological: StemEx | 18 | II |
NCT02139267 | Dose-finding, Safety Study of Plasmid DNA Therapeutic Vaccine to Treat Cervical Intraepithelial Neoplasia | Cervical intraepithelial neoplasia | Electroporation of DNA vaccine encoding for FLT3L and shuffled E6 and E7 genes of HPV type 16/18 (GX-188E) | 72 | II |
Status: Active, not Recruiting | |||||
NCT02839265 | FLT3 Ligand Immunotherapy and Stereotactic Radiotherapy for Advanced Non-small Cell Lung Cancer | Advanced non-small cell lung cancer | S.c. recombinant FLT3L (CDX-301) with stereotactic body radiotherapy | 29 | II |
NCT01811992 | Combined Cytotoxic and Immune-Stimulatory Therapy for Glioma | Malignant glioma and glioblastoma multiforme | Dose escalation of adenovirus gene transfer that drives direct tumor killing and FLT3L expression | 19 | I |
NCT02129075 | CDX-1401 and Poly-ICLC Vaccine Therapy With or Without CDX-301 in Treating Patients With Stage IIB-IV Melanoma | Stage IIB-IV melanoma | S.c. recombinant FLT3L (CDX-301), s.c. or i.d. DEC-205/NY-ESO-1 fusion protein (CDX-1401) and s.c. poly-ICLC | 60 | II |
Status: Recruiting | |||||
NCT03789097 | Vaccination With Flt3L, Radiation, and Poly-ICLC | Non-Hodgkin’s lymphoma, metastatic breast cancer and head and neck squamous cell carcinoma | In situ recombinant FLT3L, radiation and Poly ICLC with pembrolizumab | 56 * | I/II |
NCT01976585 | In Situ Vaccine for Low-Grade Lymphoma: Combination of Intratumoral Flt3L and Poly-ICLC With Low-Dose Radiotherapy | Low-grade B-cell lymphoma | In situ recombinant FLT3L (CDX-301) and poly-ICLC | 30 * | I/II |
NCT03329950 | A Study of CDX-1140 (CD40) as Monotherapy or in Combination in Patients With Advanced Malignancies | Multiple cancer types | CD40 agonist antibody (CDX-1140) alone vs. combination with recombinant FLT3L (CDX-301) vs. combination with pembrolizumab vs. combination with chemotherapy | 260 * | I |
Status: not yet Recruiting | |||||
NCT04491084 | FLT3 Ligand, CD40 Agonist Antibody, and Stereotactic Radiotherapy | Non-small cell lung cancer | FLT3L (CDX-301) with CD40 agonist antibody (CDX-1140) and stereotactic radiotherapy vs. stereotactic radiotherapy alone | 46 * | I/II |
NCT04616248 | Radio-immunotherapy (CDX-301, Radiotherapy, CDX-1140 and Poly-ICLC) for the Treatment of Unresectable or Metastatic Breast Cancer Patients | Unresectable and metastatic breast cancer | In situ FLT3L, CD40 agonist antibody (CDX-1140), poly ICLC and radiation therapy vs. addition of i.v. CDX-1140 | 36 * | I |
Status: Unknown | |||||
NCT03206138 | Safety and Efficacy of GX-188E Administered Via EP Plus GX-I7 or Imiquimod. | Cervical intraepithelial neoplasia 3 | GX-188E with GX-I7 vs. GX-188E with imiquimod | 50 * | |
NCT02411019 | Safety and Efficacy of GX-188E DNA Therapeutic Vaccine Administered by Electroporation After Observation | Cervical intraepithelial neoplasia 3 | GX-188E | 72 | II |
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Cueto, F.J.; Sancho, D. The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy. Cancers 2021, 13, 1525. https://doi.org/10.3390/cancers13071525
Cueto FJ, Sancho D. The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy. Cancers. 2021; 13(7):1525. https://doi.org/10.3390/cancers13071525
Chicago/Turabian StyleCueto, Francisco J., and David Sancho. 2021. "The Flt3L/Flt3 Axis in Dendritic Cell Biology and Cancer Immunotherapy" Cancers 13, no. 7: 1525. https://doi.org/10.3390/cancers13071525