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B. Yan
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Poster Display Session (ID 63)
- Event: ELCC 2017
- Type: Poster Display Session
- Track:
- Presentations: 2
- Moderators:
- Coordinates: 5/07/2017, 12:30 - 13:00, Hall 1
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116P - A randomized study to evaluate safety of DCVAC/LUCA added to chemotherapy with carboplatin and pemetrexed vs. chemotherapy alone in patients with stage IV non-small cell lung cancer (ID 239)
12:30 - 13:00 | Author(s): B. Yan
- Abstract
Background:
DCVAC/LuCa is an active autologous cellular immunotherapy consisting of autologous dendritic cells (DCs) loaded with NSCLC antigens (whole tumor cell antigens of tumor cell lines, like Her2/neu, MAGE-A3 and Survivin, et al.). DCVAC has the ability to induce an immune response, including cytotoxic CD8+ T cells, against tumor-associated antigens expressed by patients’ cancer cells. However, advanced-stage NSCLC with a heavy tumor burden establishes a harsh landscape for immunotherapy due to immune tolerance towards tumor antigens. Combination of DC treatment and chemotherapy is anticipated to achieve stronger immune responses than either of the treatments alone. AEs were collected in this study to evaluate the safety of DCVAC/LuCa added to chemotherapy with pemetrexed and carboplatin vs. chemotherapy alone in patients with stage IV non-small cell lung cancer.
Methods:
This is a randomized, open-label study. A total of 20 newly diagnosed stage IV, non-squamous, wild-type EGFR, ALK-negative or unknown NSCLC patients treated between January 2016- December 2016 in Shanghai Chest Hospital were enrolled.10 patients were randomized to group A: DCVAC/LuCa + chemotherapy (4-6 cycles of pemetrexed/carboplatin followed by pemetrexed as maintenance therapy); 10 patients were randomized to group B: 4-6 cycles of pemetrexed/carboplatin followed by pemetrexed as maintenance therapy.Patients in the group A started with DCVAC/LuCa (5 × 106 DCs/aliquots) treatment on Day 15 (+/- 3 days) of chemotherapy Cycle 3.The initial 5 doses of DCVAC/LCa were administered at a 3-week interval. The DCVAC/LuCa was then injected every 6 weeks up to the maximum number of 15 doses (75 × 106 DCs/15 aliquots). AEs were collected and analyzed.
Results:
The common adverse events in both group were chemotherapy related leukopenia, hemoglobin decrease etc. All AEs were grade 1 or 2 according to CTCAE V4.03, and there were no grade 4 toxicities or treatment-related deaths. One patient in group A got non-infectious fever and returned to normal without treatment.
Conclusions:
In patients with stage IV NSCLC, DCVAC/LuCa therapy was well tolerated with the favorable safety profile.
Clinical trial identification:
Legal entity responsible for the study:
Shanghai Chest Hospital
Funding:
Sotio Medical Research (Beijing) Co., Ltd
Disclosure:
All authors have declared no conflicts of interest.
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15P - PLGF regulates crosstalk between non-small cell lung cancer cells and tumor-associated macrophages in cancer vascularization and growth (ID 253)
12:30 - 13:00 | Author(s): B. Yan
- Abstract
Background:
The growth and invasion of non-small cell lung cancer (NSCLC) require assistance of tumor-associated vascularization, the underlying molecular mechanisms of which remain eluted. Recently, we reported that placental growth factor (PLGF) was expressed by NSCLC cells, and promoted the metastasis of NSCLC cells. Here, we showed that NSCLC cells produced and secreted PLGF to signal to tumor-associated macrophages (TAM) through the surface expression of the receptor for PLGF, Flt-1, on macrophages.
Methods:
Ten week-old male NOD/SCID mice were used for transplantation of 10[7] AAV-transduced/labeled A549 cells by tail vein injection. Bones from 12-week-old male C57BL/6 mice were flushed with macrophage culture media. Isolated bone-marrow-derived macrophages (10[5]) were co-cultured either with equal number of A549 cells (10[5]) with/without of 10µmol/l SB431542, or with/without recombinant PLGF (100ng), or with/without of 10 µg/l sFlt-1. Two days after co-culture, the changes in A549 cell number were determined with an MTT assay, and the macrophage subtypes were determined by flow cytometry.
Results:
In a transwell co-culture system, PLGF secreted by NSCLC cells triggered macrophage polarization to a TAM subtype that promote growth of NSCLC cells. Moreover, polarized TAM seemed to secrete transforming growth factor β 1 (TGFβ1) to enhance the growth of endothelial cells in a HUVEC assay.
Conclusions:
Thus, our studies suggest that the cross-talk between TAM and NSCLC cells via PLGF/Flt-1 and TGFβ receptor signaling may promote the growth and vascularization of NSCLC.
Clinical trial identification:
Legal entity responsible for the study:
Shanghai Chest Hospital
Funding:
This work was supported by the National Natural Science foundation of China (81402378).
Disclosure:
All authors have declared no conflicts of interest.
