Use Of Immunomodulatory Effective Kits For The Immunotherapeutic Treatment Of Patients Suffering From Myeloid Leukemias

Abstract

The present invention relates to a method for selecting an immunomodulatory kit, selected for an individual patient, for use in the treatment of patients suffering from myeloid leukemias. Different kits are available for selection and ex vivo testing which are composed of substances that have different immunomodulatory effects on leukemia cells. Each kit particularly contains GM-CSF and one (or two) more substances, selected from PICIBANIL, PGE 1 , PGE 2 , CALCIMYCIN and TNFα, as well as pharmaceutically acceptable adjuvants. The clinical aim is to modify, once the individually selected immunomodulatory kits were administered, blast cells in the body of the patient such that they turn into a “vaccine” which is able to activate the immunoreactive cells (of the patient or of the stem cell donor) in the body against blast cells.

1 - 59 . (canceled) 
     
     
         60 . Kit for use in parenteral, individual therapy and/or prevention of myelogenous leukemia in preferably immunocompetent patients in remission of the disease, containing GM-CSF and at least one further active substance selected from PICIBANIL, PGE1, PGE2, CALCIMYCIN And TNFα as well as pharmaceutically compatible active components comprising water, aqueous solutions, buffers, buffer solutions, binders and/or adjuvants, whereby myeloid leukemia is an acute myeloid leukemia, myelodysplastic disease, myeloproliferative disease or chronic myeloid leukemia. 
     
     
         61 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with 15 to 500 μg/day, preferably 75 μg/day, and PICIBANIL i.m., i.d. or s.c. with 20 to 500 μg/day, preferably 50 μg/day, whereby GM-CSF and PICIBANIL are administered in this order in a daily, two-day or three-day interval.   
     
     
         62 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with 15 to 500 μg/day, preferably 75 μg/day, and PGE1 i.v. or as a continuous infusion of 0.075 μg/kg/h, up to a maximum of 500 μg/kg/h, whereby GM-CSF and PGE1 are administered in this order in a daily, two-day or three-day interval.   
     
     
         63 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with 15 to 500 μg/day, preferably 75 μg/day, and PGE2 with 0.1 to 5 mg/kg/day, whereby GM-CSF and PGE2 are administered in this order at a daily, second-day or three-day interval.   
     
     
         64 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with up to three days with 15 to 500 μg/day, preferably 75 μg/day, and PICIBANIL i.m., i.d. or s.c. with 20 to 500 μg/day, preferably 50 μg/week, and PGE2 i.v. with 0.1 to 5 mg/kg/day, with GM-CSF, PICIBANIL and PGE2 being administered in this order in a daily, two-day or three-day interval.   
     
     
         65 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with 15 to 500 μg/day, preferably 75 μg/day, and TNFα i.v. 0.04 mg-4 mg/m2/24h, whereby GM-CSF and TNFα are administered in this order in a daily, second-day or three-day interval.   
     
     
         66 . Kit according to  claim 60 , whereby the treatment is carried out with the following dosage:
 GM-CSF as i.v. permanent infusion or daily alternating with 15 to 500 μg/day, preferably 75 μg/day, and CALCIMYCIN dosage 0.1-10 μg, whereby GM-CSF and CALCIMYCIN are administered in this order in a daily, second-day interval.   
     
     
         67 . Kit according to  claim 60  for parenteral administration 
     
     
         68 . A method for selecting a suitable kit for individual therapy and/or prevention of myelogenous leukemia, comprising the following steps:
 (A) ex vivo isolation of T cells from a sample of blast-containing or blast-free whole blood from the patient or stem cell donor;   (B) subdividing the blast-containing whole blood sample of the patient into several sub-samples;   (C) sequentially adding the following individual kits to the individual blast-containing whole blood samples at the beginning and after a first incubation period of the sub-samples, preferably 4 to 6 days, whereby leukemic blasts are converted to leukemic dendritic cells DCleu by the kits in the sub-samples:   (i) GM-CSF, PGE 2  and PICIBANIL   (ii) GM-CSF and PICIBANIL   (iii) GM-CSF and PGE 2      (iv) GM-CSF and PGE 1      (v) GM-CSF and TNFα   (vi) GM-CSF and CALCIMYCIN   (D) adding the T cells isolated in step (a) to each of the sub-samples obtained in step (c) after incubation and then incubating them during a second incubation period of preferably 7 to 10 days;   (E) performing a lysis assay in each of the sub-samples after the incubation period in step (D) for detecting the antileukemic function of the particular kit employed;   (F) creating a ranking for the kits used, depending on the quality of the result of the respective lysis tests; and   (G) selection of the kit with the best conversion of blasts into DCleu without induction of blast proliferation and the best blast lysis result obtained after antileukemic T cell activation.