20 juli 2012: dat immuuntherapie ook kan werken bij slokdarmkanker bewijst onderstaand artikel. Aan de basis van onderstaande studie lag de volgende studie: Locoregional Cellular Immunotherapy for Patients with Advanced Esophageal Cancer1  waarbij 4 van de 11 deelnemende patiënten met uitgezaaide en vergevorderde slokdarmkanker alsnog een gedeeltelijke of zelfs totale remissie bewerkstelligden. Echt een heel goed resultaat dus. Kenmerk van deze vorm van immuuntherapie is het terugbrengen direct in de tumor of in de lymfklieren van bijgekweekte T-cellen, een vorm van dendritische celtherapie ook, waarbij wel vers tumorweefsel nodig is. Onderaan staat abstract.

Cancer Sci. 2006 Jun;97(6):554-61.

Phase I/II adenoviral p53 gene therapy for chemoradiation resistant advanced esophageal squamous cell carcinoma.

Shimada H, Matsubara H, Shiratori T, Shimizu T, Miyazaki S, Okazumi S, Nabeya Y, Shuto K, Hayashi H, Tanizawa T, Nakatani Y, Nakasa H, Kitada M, Ochiai T.

Department of Frontier Surgery, Chiba University Graduate School of Medicine, 1-8-1, Inohana, Chiba, 260-8670, Japan. hshimada@faculty.chiba-u.jp

Abstract

We investigated the feasibility, safety, biological activity and therapeutic efficacy of adenovirus-mediated p53 gene transfer in patients with chemoradiation resistant advanced esophageal carcinoma. Eligible patients were not surgical candidates and had measurable, advanced squamous cell carcinoma of the esophagus that was resistant to chemoradiation therapy. On a 28-day cycle, intratumoral injections of Ad5CMV-p53 (INGN 201; ADVEXIN) were administered on days 1 and 3 at four dose levels (10 x 10(11) particles to 25 x 10(11) particles) and treated for up to five cycles. Ten patients received a total of 26 cycles with no dose-limiting toxicity. Administration of multiple courses was feasible and well-tolerated. Local tumor responses revealed stable disease in nine cases and progressive disease in one case. The overall responses were stable in six and progressive in four cases. Using polymerase chain reaction (PCR) analyses, gene transfer and p53 specific transgene expression were detected in tumor biopsy tissue from all patients. mRNA levels of p53, p21 and MDM2 increased in all but one case. Three patients showed absence of disease upon repeat biopsies. Substantial improvement in swallowing was observed in one patient with stenotic lesions. Intratumoral injection of Ad5CMV-p53 is safe, feasible and biologically active when administered in multiple doses to patients with esophageal cancer. Observations from this study indicate that this treatment results in local antitumor effects in chemoradiation resistant esophageal squamous cell carcinoma.

PMID: 16734736 [PubMed - indexed for MEDLINE]

Locoregional cellular immunotherapy for patients with advanced esophageal cancer succesfull for one third of the participating patients

Locoregional Cellular Immunotherapy for Patients with Advanced Esophageal Cancer1

  1. Kyogo Itoh

+ Author Affiliations

  1. Departments of Surgery [U. T., H. Y., S. S., T. T., F. N., H. F., K. S.] and Immunology [U. T., K. K., K. I.], Kurume University School of Medicine, Kurume 830-0011, Fukuoka, Japan

Abstract

The objectives of the present study were to determine the safety of locoregional administration of autologous lymphocytes stimulated with autologous tumor cells and interleukin (IL) 2 in vitro and to find laboratory markers to predict either clinical toxicity or clinical response. Eleven patients with advanced (n = 4) or recurrent (n = 7) esophageal cancers received the locoregional administration of these activated lymphocytes every 2 weeks for two to nine times (mean, 5.6 times), and mean numbers of the administered cells were 0.8 × 109 cells per treatment. The activated lymphocytes that were pretested for their surface markers and CTL activity were endoscopically injected into primary tumor sites (n = 4) or directly injected into metastatic lymph nodes (n = 2), pleural (n = 4) or ascitic (n = 1) regions. Grade 3 hypotension, grade 2 diarrhea, and grade 1 fever were observed in 1, 1, and 6 patients, respectively, and there was no adverse effect in the remaining three patients. The clinical outcome was as follows: one, complete response (CR); three, partial response (PR); two, stable response (SR); and five, progressive disease (PD). CTL activity in the administered cells was observed in 5 of the 11 patients (1 CR, 3 PR, and 1 PD) and was not observed in the remaining 6 patients (2 SR and 4 PD). Percentages of CD16+ cells in the peripheral blood of the responder group (CR+PR) significantly increased when compared with those before treatment or with those of the nonresponder group before as well as after treatment. Because the clinical toxicity was moderate and tolerable, this new method of locoregional immunotherapy will be applicable for use in treatment of patients with advanced and recurrent esophageal cancers. Both CTL activity in the administered cells and the percentages of CD16+ cells in the peripheral blood may be useful laboratory markers for predicting of clinical response.


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