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Methods and compositions for cancer treatment

A technology of composition and immunoconjugate, which is used in the field of cancer treatment and composition, and can solve the problems of drug resistance of chemotherapeutic agents

Pending Publication Date: 2020-05-08
SUZHOU DINGFU BIOTARGET CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In addition, patients may quickly develop resistance to chemotherapeutic agents

Method used

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  • Methods and compositions for cancer treatment
  • Methods and compositions for cancer treatment
  • Methods and compositions for cancer treatment

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Experimental program
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Embodiment approach

[0238] 1. A composition comprising an immunoconjugate and a cytotoxic agent, wherein: the immunoconjugate comprises 1) one or more interleukins, and 2) an interleukin consisting of a first Fc subunit and a second Fc subunit An Fc domain, the first Fc subunit is associated with the second Fc subunit to form a dimer; the one or more interleukins are fused to the Fc domain; wherein the cytotoxic agent is capable of inducing immunogenicity cell death.

[0239] 2. The composition of embodiment 1, wherein at least one of the one or more interleukins is fused to the amino terminal amino acid of the Fc domain.

[0240] 3. The composition according to any one of embodiments 1 to 2, wherein the immunoconjugate comprises two or more interleukins.

[0241] 4. The composition of embodiment 3, wherein at least two of the two or more interleukins are fused to the amino terminal amino acid of the Fc domain.

[0242] 5. The composition according to any one of embodiments 1 to 4, wherein one ...

Embodiment 1

[0351] Modification and preparation of embodiment 1 nucleic acid

[0352] 1.1 Fc modification

[0353] Amino acid modifications (e.g., amino acid substitutions) were made to the interface residues of the human IgG1 Fc domain to obtain the following group of modifications (as shown in Table 1 below), Chain A is also referred to as Fc9 or first Fc subunit in this application , chain B is also known as Fc6 or the second Fc subunit:

[0354]

[0355]

[0356] Table 1 Amino Acid Modification Groups

[0357] Subsequently, the ScFv-Fc / Fc system was used to examine the formation of heterodimeric proteins including the modified groups listed in Table 1 above, as detailed below.

[0358] First, the human immunoglobulin γ1 (IgG1) constant region amino acid sequence (P01857) was obtained from the database Uniprot to obtain the wild-type human IgG1-Fc region amino acid sequence (SEQ ID NO: 30). A polynucleotide fragment encoding wild-type human IgG1-Fc (SEQ ID NO: 31, named Fc gen...

example 2

[0385] Construction of Example 2 Recombinant Plasmid

[0386] The nucleic acid molecule obtained according to Example 1 (encoding Erb-Fc9, T-Fc9, 28H1-Fc9, Fc9, T-LC (trastuzumab light chain), Erb-LC (Cetol) was digested with HindIII and EcoRI (Takara). Cyximab light chain), 28H1-LC, (IL10) 2 -Fc6 and IL10-Fc), followed by subcloning into the vector pcDNA4 / myc-HisA (Invitrogen, V863-20) respectively. The obtained plasmids were verified by sequencing, and the correct recombinant plasmids were named: pcDNA4-Erb-Fc9, pcDNA4-T-Fc9, pcDNA4-28H1-Fc9, pcDNA4-Fc9, pcDNA4-T-LC, pcDNA4-Erb-LC , pcDNA4-28H1-LC, pcDNA4-(IL10) 2 - Fc6 and pcDNA4-IL10-Fc.

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Abstract

Provided are compositions and methods for treating cancer comprising the use of aimmunoconjugate in combination with a cytotoxic agent or cytotoxic therapy. The immunoconjugate in combination with a cytotoxic agent or cytotoxic therapy shows synergistic effects in cancer treatment.

Description

Background technique [0001] Although immune responses against tumor antigens can be detected (Disis et al. (1997) J. Clin. Oncol. 15:3363-3367), disease-causing malignant cells are often unable to elicit immune responses that lead to rejection. Studies have demonstrated that tumor cell immunogenicity can be enhanced by introducing immunomodulatory molecules (such as cytokines) and co-stimulatory molecules to tumor cells; however, eradication of residual cancer cells may require targeting widely dispersed micrometastatic tumor deposits , said deposits are inaccessible by direct gene transfer. Furthermore, the expression and stability of the introduced immunomodulatory molecules are often not satisfactory. Immunomodulatory factors (such as cytokines) produced by cells of the immune system can directly or indirectly activate cells with adaptive immune responses and can play an important role in eliciting protective anti-tumor immunity. The innate immune system can be triggered ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07K14/54C07K19/00
CPCC07K14/54C07K14/5428C07K19/00C07K2319/30C07K2319/33A61K38/20C07K16/2863C07K2317/52C07K2317/622C07K2317/569C07K16/32C07K16/40A61P35/00A61K2039/505A61K47/6813A61K45/06
Inventor 徐霆栾彦傅士龙秦颂兵丁健付凯
Owner SUZHOU DINGFU BIOTARGET CO LTD
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