Target intelligence / Profile preview

Immunoglobulin kappa constant region (IGKC) (IGKC)

Target
IGKC
Molecular classification
Immunoglobulin, Constant region
01

Overview

The Immunoglobulin kappa constant region (IGKC) is the invariant portion of the kappa light chain in antibodies and B-cell receptors (UniProt: P01834). In humans, B-cells express either a kappa or a lambda light chain, a phenomenon known as allelic exclusion (PubMed: 26239086). This makes IGKC an attractive therapeutic target for B-cell malignancies, such as multiple myeloma and non-Hodgkin lymphoma, where the tumor is often restricted to a single light chain type (PubMed: 31515258). By targeting IGKC, therapies like CAR-T cells can selectively eliminate the malignant kappa-positive B-cell population while sparing lambda-positive B-cells, thereby preserving a degree of humoral immunity (ClinicalTrials.gov: NCT04440631). This approach aims to reduce the profound immunosuppression typically seen with pan-B-cell targets like CD19 or CD20. Additionally, IGKC is a critical biomarker in the diagnosis and monitoring of plasma cell dyscrasias through the measurement of free light chain ratios (PubMed: 19300231).

Other names
IGKCIg kappa chain C regionImmunoglobulin kappa constantHCAK1Km antigen
02

Mechanism of action

Targeted depletion of B-lineage cells expressing the kappa light chain, preserving lambda-expressing B-cells to maintain partial humoral immunity (PubMed: 31515258).

03

Biological functions

Immune responseAntigen bindingHumoral immunity
04

Disease associations

Multiple myelomaAL amyloidosisB-cell lymphomaMonoclonal gammopathy
05

Safety considerations

B-cell aplasiaHypogammaglobulinemiaCytokine release syndromeOff-tumor toxicity
06

Interacting drugs

IGKC-directed CAR-T cells

1 more in the full profile.

07

Biomarkers

Serum free light chain (sFLC) ratioKappa/lambda ratioClonality assessment

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