Start Your Search
MA09 - Immunotherapy Combinations (ID 390)
- Event: WCLC 2016
- Type: Mini Oral Session
- Track: Chemotherapy/Targeted Therapy/Immunotherapy
- Presentations: 1
MA09.07 - Phase I Trial of in situ Vaccination with CCL21 Gene-Modified DC Induces Specific Systemic Immune Response and Tumor Infiltrating CD8<sup>+</sup> T Cells (ID 4917)
14:20 - 15:50 | Author(s): J. Yanagawa
Intratumoral (IT) infiltration by activated immune effector cells is associated with a significantly better prognosis, however, tumor-associated immune suppression commonly occurs in non-small cell lung cancer (NSCLC). CD8[+ ]T cell or dendritic cell (DC) infiltration is an independent favorable prognostic indicator. CCL21 is a lymphoid chemokine that chemoattracts both lymphocytes and DC. Our aim was to investigate anti-tumor specific systemic immune responses and tumor-infiltrating CD8[+] T cells (CD8[+] TIL) in NSCLC patients in response to in situ vaccination via IT administration of autologous DC transduced with a replication-deficient adenoviral (Ad) vector expressing the secondary lymphoid chemokine (SLC/CCL21) gene. Here, we conducted a phase I trial and evaluated safety and immune responses following in situ vaccination.
Sixteen stage IIIB/IV NSCLC subjects received two vaccinations (1 x 10, 5 x 10, 1 x 10, or 3 x 10 dendritic cells/injection) by CT- or bronchoscopic-guided IT injection (days 0 and 7). Immune responses were assessed by tumor antigen-specific peripheral blood lymphocyte induction of IFN-γ in ELISPOT assays. Tumor biopsies were evaluated for CD8[+ ]T cells by immunohistochemistry (IHC).
Twenty-five percent (4/16) of patients had stable disease at day 56 follow-up by RECIST criteria. Median survival was 3.9 months. Four possible vaccine-related grade 1 adverse events (AE) occurred in 3 patients with no clear association to dose or schedule; the AE included flu-like symptoms, blood-tinged sputum after each injection, nausea, and fatigue. ELISPOT assays revealed 38% (6/16) of patients had systemic responses against tumor associated antigens (TAA). Tumor CD8[+] T cell infiltration was induced in 54% of subjects (7/13; 3.4 fold average increase in the number of CD8[+ ]T cells per mm). Patients with increased intratumoral CD8[+ ]T cells following vaccination showed significantly increased PD-L1 mRNA expression (p=0.02).
Intratumoral vaccination with Ad-CCL21-DC was well-tolerated and resulted in 1) induction of systemic tumor antigen-specific immune responses and 2) enhanced tumor CD8[+ ]T cell infiltration. DC-CCL21 in situ vaccination may be a promising approach to induce tumor CD8[+ ]T cell infiltration in combination with checkpoint inhibitor therapy.
Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.