Publication Date:
2010-11-19
Description:
Abstract 286 Background: In a murine model, our in situ vaccination therapy combining tumor antigens with TLR9 agonist cured mice of lymphoma. Our phase I/II study in indolent B-cell lymphoma demonstrated that this in situ vaccination maneuver utilizing local radiation to expose tumor antigens combined with CpG ODN was well-tolerated without treatment limiting toxicities. It induced meaningful systemic clinical responses and tumor-reactive memory CD8 T-cells. In parallel, we explored this in situ vaccination strategy in cutaneous T-cell lymphoma (CTCL), specifically mycosis fungoides (MF). Our objectives were to determine the feasibility and safety and to assess the local and systemic antitumor effects in MF. Methods: Patients with MF stages IA-IVA who failed ≥1 standard therapy were eligible. Immunization site was treated with low-dose radiation (2 Gy × 2 d), bracketed by intratumoral injection of CpG followed by weekly intratumoral CpG × 8. Local (immunized site) and systemic antitumor responses were assessed at wk 0, 2, 4, 8, 12, then monthly until PD/off-study. Clinical response was evaluated by assessing skin disease burden at sites not treated with immunization procedure. Results: Study enrollment was completed with total of 15 patients. Median age was 57 yrs (range 18–71 yrs), 12 of 15 were male. Six patients had stage IB and 9 with stage IIB (3 with large-cell transformation). Median number of prior therapies was 5 with range of 2–9. After the initial 6 patients, a second immunization site was added at wk 4 to enhance systemic response. Total of 5 partial responses were observed (30% OR); 2 of 6 treated with single immunization and 3 of 9 with dual immunization. Median time to response was 8 wks (range 4–12 wks), duration of response 7 wks (range 4–44 wks), and time to progression 20+ wks (range 3–44+ wks). Patients with large-cell transformed MF did not respond. Common toxicities were injection site and flu-like symptoms; mostly grade 1–2 and all transient. No clinical or laboratory findings of any autoimmune disorder were observed. Local tissue tumor/immune responses were assessed by immunostaining. CpG + local radiation treated immunization site showed a significant reduction of CD25+, Foxp3+ T-cells (p
Print ISSN:
0006-4971
Electronic ISSN:
1528-0020
Topics:
Biology
,
Medicine
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