title: In situ vaccination against mycosis fungoides by intratumoral injection of a TLR9 agonist combined with radiation: a phase 1/2 study.
abstract: We have developed and previously reported on a therapeutic vaccination strategy for indolent B-cell lymphoma that combines local radiation to enhance tumor immunogenicity with the injection into the tumor of a TLR9 agonist. As a result, antitumor CD8(+) T cells are induced, and systemic tumor regression was documented. Because the vaccination occurs in situ, there is no need to manufacture a vaccine product. We have now explored this strategy in a second disease: mycosis fungoides (MF). We treated 15 patients. Clinical responses were assessed at the distant, untreated sites as a measure of systemic antitumor activity. Five clinically meaningful responses were observed. The procedure was well tolerated and adverse effects consisted mostly of mild and transient injection site or flu-like symptoms. The immunized sites showed a significant reduction of CD25(+), Foxp3(+) T cells that could be either MF cells or tissue regulatory T cells and a similar reduction in S100(+), CD1a(+) dendritic cells. There was a trend toward greater reduction of CD25(+) T cells and skin dendritic cells in clinical responders versus nonresponders. Our in situ vaccination strategy is feasible also in MF and the clinical responses that occurred in a subset of patients warrant further study with modifications to augment these therapeutic effects. This study is registered at www.clinicaltrials.gov as NCT00226993.
authors: Department of Dermatology, Stanford University School of Medicine, CA, USA. younkim@stanford.edu
authors: Youn H
authors: YH
authors: Kim
authors: Dita
authors: D
authors: Gratzinger
authors: Cameron
authors: C
authors: Harrison
authors: Joshua D
authors: JD
authors: Brody
authors: Debra K
authors: DK
authors: Czerwinski
authors: Weiyun Z
authors: WZ
authors: Ai
authors: Anjali
authors: A
authors: Morales
authors: Farah
authors: F
authors: Abdulla
authors: Leon
authors: L
authors: Xing
authors: Daniel
authors: D
authors: Navi
authors: Robert J
authors: RJ
authors: Tibshirani
authors: Ranjana H
authors: RH
authors: Advani
authors: Bharathi
authors: B
authors: Lingala
authors: Sumit
authors: S
authors: Shah
authors: Richard T
authors: RT
authors: Hoppe
authors: Ronald
authors: R
authors: Levy
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005240:Feasibility Studies; D005260:Female; D005455:Fluorescent Antibody Technique; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D015552:Injections, Intralesional; D007801:Langerhans Cells / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009182:Mycosis Fungoides / Q000276:immunology* / Q000532:radiotherapy*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D011379:Prognosis; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D051217:Toll-Like Receptor 9 / Q000819:agonists* / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination; D055815:Young Adult
chemical_list: D019496:Cancer Vaccines; C526902:CpG ODN 2216; D009838:Oligodeoxyribonucleotides; D051217:Toll-Like Receptor 9