Anti-Human CD19 (Clone 4G7) – Purified in vivo GOLD^TM Functional Grade

Mouse IgG1 GOLD, Clone hksp OR Mouse IgG1 GOLD, Clone hksp84

Human Chronic Lymphocytic Leukemia (CLL) cells

This monoclonal antibody is aseptically packaged and formulated in 0.01 M phosphate buffered saline (150 mM NaCl) PBS pH 7.2 - 7.4 with no carrier protein, potassium, calcium or preservatives added. Due to inherent biochemical properties of antibodies, certain products may be prone to precipitation over time. Precipitation may be removed by aseptic centrifugation and/or filtration.

Liquid

Functional grade preclinical antibodies are manufactured in an animal free facility using only in vitro protein free cell culture techniques and are purified by a multi-step process including the use of protein A or G to assure extremely low levels of endotoxins, leachable protein A or aggregates.

Functional grade preclinical antibodies may be stored sterile as received at 2-8°C for up to one month. For longer term storage, aseptically aliquot in working volumes without diluting and store at ≤ -70°C. Avoid Repeated Freeze Thaw Cycles.

Research Use Only

2 – 8° C Wet Ice

FA
IF
FC
CARs

4G7 activity is directed against human CD19.

CD19 is a B cell surface glycoprotein that is a member of the immunoglobulin (Ig) superfamily^{1, 2}. CD19 is a positive regulator of B cell differentiation that also acts as a bridge between the innate and adaptive immune responses ². Additionally, CD19 enhances B cell receptor signaling and tumor cell proliferation 1¹.

B cell differentiation occurs in the bone marrow and follows a progression from hematopoietic stem cells to ProB, PreB, and then immature B lymphocytes³. The progression involves multiple gene rearrangements that are carefully controlled and results in the generation of the basic Ig repertoire and expression of various surface molecules, including CD34, CD10, and CD19 ³, which forms a complex with Leu13, CD81, and CD21 on the surface of mature B cells ². Additionally, CD19 associates with the B cell antigen receptor to enhance signal transduction ². CD19 is an attractive immunotherapy target for cancers of lymphoid origin due to its early and persistent expression throughout B cell maturation⁴.

4G7 was generated by immunizing a mouse with chronic lymphocytic leukemia cells ⁵. The antibody is specific for normal and malignant B lymphocytes. 4G7 has been used to analyze CD19 variants for the development of improved CD19 CAR T cell immunotherapy ⁶ and for fine mapping of the binding epitope ⁷. The 4G7 epitope is conformationally sensitive and is not accessible on wildtype CD19 when displayed on yeast cells ⁷ but is available on a mutated variant, CD19.1 ⁶. The 4G7 epitope centers around residue R144, and the hot spot for impactful mutations lies between residues 138 and 153. Additionally, a properly folded extracellular domain is required for 4G7 binding. A single chain Fv fragment of 4G7 has also been tested for bispecific CD19 immunotherapy development ^{8, 9}.

CD19 is a surface antigen present on all B cells (healthy and malignant) except hematopoietic stem cells and plasma cells; it is highly conserved in B cell malignancies.

Forms complex with CD21 (CR2) and CD81 (TAPA-1), BCR coreceptor

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2. Del Nagro CJ, Otero DC, Anzelon AN, et al. Immunol Res. 31(2):119-131. 2005.
3. Lemmers B, Gauthier L, Guelpa-Fonlupt V, et al. Blood. 93(12):4336-4346. 1999.
4. Horton HM, Bernett MJ, Pong E, et al. Cancer Res. 68(19):8049-8057. 2008.
5. Meeker TC, Miller RA, Link MP, et al. Hybridoma. 3(4):305-320. 1984.
6. Klesmith JR, Su L, Wu L, et al. Mol Pharm. 16(8):3544-3558. 2019.
7. Klesmith JR, Wu L, Lobb RR, et al. Biochemistry. 58(48):4869-4881. 2019.
8. Kügler M, Stein C, Schwenkert M, et al. Protein Eng Des Sel. 22(3):135-147. 2009.
9. Kang CH, Kim Y, Lee HK, et al. Int J Mol Sci. 21(23):9163. 2020.
10. Williams NB, Batool S, Zumrut HE, et al. Biochemistry. 61(15):1600-1613. 2022.
11. Hörner S, Moustafa-Oglou M, Teppert K, et al. Cancers (Basel). 14(16):3941. 2022.