Combined Thalidomide and Recombinant Human Interferon-α-1b and Interleukin-2 for Acute Myeloid Leukemia of Various Disease Status: A Multi-Center Prospective Study

AML (acute myeloid leukemia) patients with relapsed refractory diseases or in poor physical conditions have very limited choices of appropriate treatment regimens, and most alternative options are costly. Here, we reported that an affordable regimen with combined recombinant human interferon-α-1b (IFN-α1b), thalidomide, and recombinant interleukin-2 (IL-2) (the ITI regimen) achieved varying degrees of therapeutic effects in AML patients of various disease status and vulnerabilities. ITI regimen was administrated as follow: a subcutaneous injection of IFN-α1b 60 μg qod, IL-2 1 million unit qod, and 200mg thalidomide tablet orally taken every night before sleep. Group A Sixty-eight patients who were with relapsed or refractory AML were enrolled, sixty finished at least one course, a response rate (CR+CRi) of 16.7% (10/60) was observed, and, and 7 (11.7%) patients achieved partial remission.(Table 1) Group B Eighteen patients with morphologically complete remission and consistently positive MRD were enrolled, each patients underwent ITI regimen for 2 months at least. According to the criteria of the WHO risk stratification, 7 were with a favorable risk, 8 were with a intermediate risk, and 3 were with a high risk. Patients with FLT3-ITD mutations were treated with oral sorafenib during early induction and consolidation treatment. These 18 patients received conventional dosage of ITI regimen. Seven patients had a negative MRD after 1 or 2 months. The MRD levels of 3 patients significantly decreased after one or two months. Five patients suffered a Morphological relapse. Another 3 patients failed to the conventional dosage of ITI regimen with an increased MRD rate, but it decreased after we made a modification of IFN-α1b and IL-2 administration daily. The response rate of the 18 patients in Group B was 72.2%, where MRD < 0.01% was defined as the negative threshold. (Table 2) Group C Eighty-eight patients with MRD-negative AML after consolidation were enrolled. Among the 88 patients with initial CR, 11 (12.5%) relapsed during the maintenance period (Figure 1). All these 11 patients relapsed within 2 years, with a median recurrence period of 20 months, of which 2, 4, and 5 patients, respectively, were with favorable, intermediate, and high risk. The indicated that this regimen effectively reduced the relapse rate.(Table 3) Disclosures No relevant conflicts of interest to declare.

Development of Fusion Protein Produce Technology Based on a Humanized Monoclonal Antibody Specific to Tumor Antigen HER2 and a Recombinant Human Interferon-α-2b in Nicotiana benthamiana

Fusion proteins based on a recombinant human interferon-α-2b and a humanized monoclonal antibody specific to tumor antigen HER2 have been obtained by transient expression in Nicotiana benthamiana. To provide an effective expression and a proper immunocytokine molecule assembly the genetic constructs optimization was performed. The expression level was shown to depend on the linker length between the cytokine and the antibody moieties in the hybrid molecule. The modification of the interferon domain sequence by replacing cysteine residues with serine showed a slight increase in the production level of the target protein. The assembly of full-size fusion protein molecules was confirmed by the qualitative method of «combined ELISA» developed by the authors. The preservation of the affine domain function in the fusion proteins was proved by the ELISA method in interaction with the antigen. interferon- α-2b, antigen HER2, plant transient expression, recombinant fusion proteins.