Helge Bartsch

Intralesional application of recombinant human tumor necrosis factor alpha induces local tumor regression in patients with advanced malignancies

Fourteen patients with different advanced solid tumors were treated by intratumoral application of recombinant human tumor necrosis factor alpha. In five patients, local tumor regression occurred. However, the duration of response was short, implying a rapid development of resistance to rTNF-alpha application. The main clinical side-effects, including chills, fever, anorexia and fatigue, were similar to systemic rTNF-alpha treatment. Cardiovascular, pulmonary or metabolic toxicities were not observed. This study demonstrates that a high concentration of rTNF-alpha at the tumor site has the potential to induce local tumor regressions and, therefore, seems more reasonable for further clinical investigations, especially in combination with other cytokines.

Systemische versus lokale Therapie mit rekombinantem Tumor-Nekrose-Faktor-alpha (r-TNF-alpha) bei Patienten mit fortgeschrittenen Tumoren

Im Rahmen von zwei Phase-I-Prufungen wurde rekombinanter Tumor-Nekrose-Faktor-alpha (rTNF-alpha) zur Behandlung von 44 Patienten mit fortgeschrittenen Tumoren unterschiedlichster Histologien eingesetz

IFN-γ Receptors on Human Tumor Cells: Relationship between Receptor Ligand Interactions and Induction of IFN-γ Response

Abstract Scatchard analysis of 125 I-IFN-³ binding on fresh lymphoid and myeloid tumor cells derived from 34 leukemia patients and on normal cells obtained from 14 healthy individuals revealed similar high affinity binding with a mean Kd of around 2 x 10 -11 M in 14/14 normal and 30/34 malignant cells, but large quantitative differences in the receptor number of malignant cells with a range of 300 to 12,000 receptors/cell. In contrast, normal lymphoid and myeloid cells expressed consistantly low numbers of receptors with a mean of 300 and 1,000 receptors/cell, respectively. Kinetic studies of IFN-γ binding in relation to induction of HLA-DR antigens in established cell lines revealed the existence of close correlations between the quantity of receptor ligand interaction and induction of IFN-γ response, indicating that at limiting IFN-γ concentrations the height of response is controlled by the number of expressed membrane receptors. In the light of the observed quantitative differences in IFN-γ receptors on various tumors, this finding may have implications for the definition of therapeutically effective IFN-γ doses.

Rearrangements of T cell receptor genes and expression of high affinity IL-2 receptors in an EBV transformed B cell line

The study is based on the observation of 584 patients (pts) with malignant lymphomas (Morbus Hodgkin 248, Non Hodgkin Lymphoma of favorable histology 2o3, of unfavorable histology 133), who had regular follow ups from 1974-1983. 315 of these pts attained a complete remission( 169, 64,82 respectively). Io8 pts suffered from a relapse (61,22,25). 68% of these pts had symptoms directing to the relapse (62,77,76%). 33% palpated the tumor themselves (36,41,2o%). 2o% showed specific symptoms like local pain or lymphedema (13,13,44%). 15% suffered from general symptoms like B-symptoms (13,13,12%). Regarding the 32% of the pts without symptoms: the relapse was diagnosed by clinical examination in Io%(11, 9,8%). ~fne routinely taken chest x ray showed the relapse in 8% (Io,9,4%), the sonography in 7% (Io,5,4%). in 6% the relapse was discovered by other investigations (7,o,8%). At the time of the relapse the following laboratory findings were striking: 49% of pts with M. H. had a leucocytesis, in 7o% an elevated ESR, in 58% the alpha-2-globulin fraction was increased over Io%. Pts with unfavorable ~L showed in 6o% an elevated ESR and LDH, in 46% the alpha-2-globulin fraction was increased. Our study shows that the history and the clinical examination are the most important parameter recognizing a relapse. Chest x ray and sonography show only in 8 or 7% the relapse. The laboratory findings are less important except the ESR, the LDH and the alpha-2-globulin fraction.