Thierry Philip

Recombinant Human Interleukin-2, Recombinant Human Interferon Alfa-2a, or Both in Metastatic Renal-Cell Carcinoma

Background Recombinant human interleukin-2 (aldesleukin) and recombinant human interferon alfa can induce notable tumor regression in a limited number of patients with metastatic renal-cell carcinoma. We conducted a multicenter, randomized trial to determine the effect of each cytokine independently and in combination, and to identify patients who are best suited for this treatment. Methods Four hundred twenty-five patients with metastatic renal-cell carcinoma were randomly assigned to receive either a continuous intravenous infusion of interleukin-2, subcutaneous injections of interferon alfa-2a, or both. The main outcome measure was the response rate; secondary outcomes were the rates of event-free and overall survival. Predictive factors for response and rapid progression were identified by multivariate analysis. Results Response rates were 6.5 percent, 7.5 percent, and 18.6 percent (P<0.01) for the groups receiving interleukin-2, interferon alfa-2a, and interleukin-2 plus interferon alfa-2a, respectiv...

Chromosome study of Ewing's Sarcoma (ES) cell lines. Consistency of a reciprocal translocation t(11;22)(q24;q12)

A detailed banded chromosome analysis was performed in five established Ewings sarcoma (ES) cell lines originating from four unrelated patients in relapse. Of various numerical and structural abnormalities, a reciprocal translocation between chromosomes #11 and #22, t(11;22)(q24;q12), was observed in four of the lines. The t(11;22) was seen in every cell in three lines; in the fourth, it was seen in only 21% of the cells considered stemline, but the der(22) was present in the remaining 79% of cells. These results suggest that t(11;22)(q24;q12) is a chromosomal change specific to ES cells, in which the rearrangement of chromosome #22 could be the consistent karyotypic feature and the crucial step in terms of cell proliferation. Other, nonrandom chromosomal changes were found: monosomies 2p11----2pter, 10q25----10qter, and 17pter----17q11, and partial trisomies 1q21----1q31 and 8q24.1----8q24.2. The role of the therapeutic regimen received by these patients must be evaluated with regard to the formation of a wide variety of homogeneously staining regions, which were observed in every cell line, particularly on the short arm of chromosome #7, which was observed in three of the five cell lines.

Definition of response and remission in children over one year of age with advanced neuroblastoma: proposition for a scoring system.

A two-step evaluation system is proposed to analyze the results of therapy for stage IV neuroblastoma in children over 1 year of age. Since most protocols consist of first-line chemotherapy followed by surgery and often high-dose chemotherapy with bone marrow rescue, response should assess the effect of chemotherapy alone and remission indicate the status after an attempt to remove the primary tumor. A scoring system is proposed for both steps. The comparability of different studies depends on the use of such common criteria to define patient groups and treatment results.

Use of a liquid cell culture assay to quantify the elimination of Burkitt lymphoma cells from the bone marrow.

A new liquid cell culture assay for propagating Burkitt lymphoma (BL) cells in the presence of excess allogeneic irradiated bone marrow (BM) has been standardized. The Burkitt cell lines used in this assay were newly established from the tumours of our patients and were either EBV(+) or EBV(-). The phenotypic characteristics of lines were similar to those of the original malignant tumours. With the help of this liquid assay it was possible to evaluate the efficacy of in vitro procedures designed to completely eliminate malignant cells from harvested BM prior to autologous transplantation (i.e., immunomagnetic depletion or antibody-complement-mediated cytolysis). With six out of the seven cell lines tested, the assay permitted the detection of as few as one BL cell in 4 X 10(6) normal BM cells and the measurement of up to 5 log BL cell elimination from 1% contaminated samples.

Purging procedures: a critical step in autologous bone marrow transplantation

Autologous bone marrow transplantation (ABMT) provides an effective method of preventing prolonged or permanent aplasia after intensive chemoradiotherapy. Many of the solid tumors in which such ‘massive therapy’ may be effective, however, metastasize to the marrow and for this reason, although marrow is generally harvested during clinical complete remission (CR), there remains concern about the possibility of reinfusing malignant cells.

Interleukin-2 and lymphokine activated killer (LAK) cells

Lymphokine-activated-killer cells are peripheral lymphocytes that develop, following exposure to Interleukin-2 (IL2), the ability to lyse tumour cells but not normal cells. This phenomenon has been extensively studied in the early eighties. These LAK cells appeared cytotoxic to non-cultured, natural killer-cell-resistant tumour cells without antigenic stimulation implicating killing in a non MHC-restricted manner [1, 2]. Extensive studies of the precursors of LAK cells have revealed that they are constituted in part of activated cytotoxic T cells but consist predominantly of activated Natural-Killer (NK) cells [3,4].

Adoptive Immunotherapy with Interleukin-2 and LAK Cells or Gene Modified TIL in Patients with Renal Cell Carcinoma: Clinical and Laboratory Data

Approximately half of the patients diagnosed with renal cell carcinoma (RCC) develop metastases and have a median survival of 8 months. Metastatic renal cancer is considered a tumor resistant to conventional therapies, and therefore, the role of immunotherapy in this disease has been explored. Since 1984, Interleukin-2 (IL-2) has been widely used in oncology and is now registered for use in patients with metastatic renal cell carcinoma in various European countries and the USA. However, although rIL-2 is now generally accepted as an integral part of the management of metastastic renal cell carcinoma, its optimal application is still a matter for debate.