Seta Clinic Group, MEDINET’s Contracted Medical Institutions, Treatment

(Extracts from　Immuno-cell therapy of cancer in Japan; Egawa K.; Anticancer Research, 24; 3321-3326, 2004)

In 1999, Seta Clinic was established in Tokyo as the first private clinic specializing in immuno-cell therapy, followed by several other clinics. Thus, the number of patients who underwent the therapy increased very rapidly. Seta clinic has extended to form a group with three other independent clinics. Each of them is equipped with aseptic rooms for cell culture and a common standard operation manual. The assurance of safety is carried out by self-regulation of the clinics in accordance with good manufacturer' practice guidelines applied on production of pharmaceutical materials.
Our experience in two leading clinics of the group (established in 1999 and in 2001) is summarized in Tables V and VI. In these clinics, 1401 patients had received more than 6 infusions of autologous activated lymphocytes before the end of 1993. The patients included patients with various tumors. With a very few exceptions, they were all in stage IV. Tumor sizes of 809 patients of the 1401 were not measurable by X-ray examinations. The efficacy of the therapy was evaluated by the changes in tumor sizes measured before and after the therapy. The evaluation was carried out according to the criteria of evaluation of the efficacy of chemotherapy. Of the 592 patients whose tumor size could be measured, more than half received the lymphocyte infusion alone without any standard therapies. Most of the patients in this group had malignancies that failed to respond to any of the standard therapies.
In these clinics, four types of autologous activated lymphocyte therapy shown in Table V have been performed. Nearly 90 % of the patients received CD3-LAK therapy; other patients received therapies in which specific antigenic stimulation was carried out. Because of the difference between the backgrounds of patients studied, noconclusion can be drawn from the comparison of the efficacy rates of the two groups. However, the results suggest that there is a tendency for the therapy to be particularly effective when combined with standard therapies in the latter gorup. The efficacy rate obtained from the 529 patients is 15 % when PNC is not included and 26 % when it is included. In both cases, the group treated with a combination of immuno-cell therapy and standard therapy showed higher efficacy rate than the group treated with immuno-cell therapy alone. The overall efficacy rate of the therapy when PNC is included in the responsive patients is 31 %. Although the efficacy rates were obtained in retrospective studies, some suggestions about the usefulness and limitation of the therapy seem to have been obtained because the number of the patients studied was large. The efficacy rate and the absence of harmful side-effects seem to support the view that the therapy is beneficial to patients with advanced cancer.

Table V Patients who received more than 6 times repeated administration of autologous activated lymphocytes in Seta Clinic (1999~2003) and Shinyokohama Medical Clinic (2001~2003)

Total number of patients 1401
Number of non-evaluable patients	809 (57.7 %)
Number of evaluable patients	592 (42.3 %)
Immuno-cell therapy alone	284 (48.0 %)
Immuno-cell therapy in combination with chemotherapy or radiation therapy	308 (52.0 %)

Therapy on the evaluable patients
CD3-LAK　 1）	526 (88.9 %)
CTL　2）	20 (3.4 %)
DC-CTL　3）	8 (1.4 %)
DC+LAK 　4）	38 (6.4 %)

• 1) Lymphocytes are stimulated with immobilized CD3 antibody and IL-2.
• 2) Lymphocytes were stimulated with autologous tumor cells and then with immobilized CD3 antibody and IL-2.
• 3) Lymphocytaes were stimulated with autologous dendritic cells pulsed with tumor lyste or with antigenic peptides and then with immobilized CD3 antibody and IL-2.
• 4) Autologous dendritic cells as in 4） are administered as therapeutic vaccine together with administration of lymphocytes as in 1)

Table VI Efficacy of autolougous activated lymphocyte therapy (summary of results obtained in Seta clinic during 1999~2003 and in Shinyokohama Medical Clinic during 2001~2003)

(A) Basis of calculation	Efficacy rate (%)

Total of 592 evaluable cases
Including prolonged NC in effective cases
Total	26
Immuno-cell therapy alone	20
Immuno-cell therapy in combinatined with chemotherapy or radiotherapy	31
Not including prolonged NC in effective cases
Total	15
Immuno-cell therapy alone	9
mmuno-cell therapy in combination with chemotherapy or radiotherapy	21

(B) Type of autologous activated lymphocyte therapy Efficacy rate including	Prolonged NC

CD3-LAK (526 cases)
Total	25
Immuno-cell therapy alone	21
Immuno-cell therapy in combination with Chemotherapy or radiotherapy	28
(CTL + DC-CTL + DC+LAK ) (66 cases in total)
Total	36
immuno-cell therapy alone	14
mmuno-cell therapy in combination with chemotherapy or radiotherapy	50