How does the calicheamicin payload work?

Calicheamicins are DNA cleaving agents. They bind with DNA in the minor groove in a relatively sequence-specific manner. Once bound, they cause strand scission, which leads to cell death. They are structurally distinct from tubulin inhibitors like auristatins.

What type of linker connects the antibody and toxin?

This product utilizes an acetyl butyrate linker. It is designed to facilitate the release of the calicheamicin payload. The specific chemistry allows for the targeted delivery of the DNA-damaging agent to CD33-positive cells, such as those found in AML.

Anti-CD33 (hP67.6 )-calicheamicin ADC (gemtuzumab ozogamicin)

CAT#: ADC-L025

This ADC product is composed of an anti-CD33 antibody (clone hP67.6 ) conjuagated to calicheamicin (hP67.6-calicheamicin). It has demonstrated a response in AML treatment by a MOA (Mechanism of Action) of Calicheamicins target DNA and cause strand scission. Calicheamicins bind with DNA in the minor groove.

Gene Expression

Subcellular Location and Protein Expression Figure 1 IF staining of human cell line PC-3

Immunofluorescent staining of human cell line PC-3 shows localization to nucleoplasm & plasma membrane.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1186_A4_3_selected.jpg

Subcellular Location and Protein Expression Figure 2 IHC staining of human lymph node

Immunohistochemical staining of human lymph node shows membranous and cytoplasmic positivity in germinal center cells and non-germinal center cells.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/35832/113039_A_9_8_selected.jpg

Subcellular Location and Protein Expression Figure 3 IHC staining of human tonsil

Immunohistochemical staining of human tonsil shows cytoplasmic positivity in germinal center cells and non-germinal center cells.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/11442/26430_A_6_8_selected.jpg

Subcellular Location and Protein Expression Figure 4 IF staining of human cell line RH-30

Immunofluorescent staining of human cell line RH-30 shows localization to nucleoplasm.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1413_G6_1_red_green.jpg

Subcellular Location and Protein Expression Figure 5 IF staining of human cell line U-2 OS

Immunofluorescent staining of human cell line U-2 OS shows localization to nucleoplasm.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/64807/1200_A4_2_red_green.jpg

Normal Tissue Figure 6 Kidney

Cells in tubules
Staining:Medium
Intensity: Strong
Quantity: <25%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_A_9_5.jpg

Normal Tissue Figure 7 Lymph node

Non-germinal center cells
Staining:Medium
Intensity: Strong
Quantity: <25%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_A_9_8.jpg

Normal Tissue Figure 8 Spleen

Cells in red pulp
Staining:Medium
Intensity: Moderate
Quantity:>75%
Location: Cytoplasmic/membranous

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/images/79996/170702_B_8_4.jpg

RNA Expression Figure 9 RNA cell line category: Cell line enhanced (HEL, HL-60, HMC-1, NB-4, RPMI-8226, THP-1, U-937)

Cell lines ordered by descending RNA expression order.

* Image credit: Image credit: Human Protein Atlas https://v21.proteinatlas.org/ENSG00000105383-CD33

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Specifications

Antibody Overview
Humanized IgG4k antibody hP67.6 (Anti-CD33)

Clone
hP67.6

Antibody Conjugation
Humanized

Linker
acetyl butyrate linker

Drug
calicheamicin

Drug Class/Description
Class: Calicheamicin
Description: Calicheamicin, produced by prokaryotic microorganisms, are a group of DNA cleaving agents with similar structure that binds in the minor grove of DNA in a relatively sequence-specific manner.

Target

Introduction
CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

Alternative Names
CD33; CD33 molecule; p67; SIGLEC3; SIGLEC-3

Gene ID
945

UniProt ID
P20138

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Breast cancer biomarkers at key points during disease progression

Potent DNA Cleaving Agent

We investigated the effects of Calicheamicin conjugated to the anti-CD33 clone hP67.6. The ability of Calicheamicin to bind the minor groove of DNA and cause strand scission makes this a very potent tool for our AML cell line studies. The mechanism of action is distinct and highly effective in our assays.

Myeloid Specific Targeting

The humanized antibody hP67.6 shows excellent specificity for CD33, a transmembrane receptor on myeloid cells. This specificity, combined with the acetyl butyrate linker, allows us to precisely target our cell populations of interest. The product performance has been consistent across multiple replicates in our lab.

Q&As

How does the calicheamicin payload work?

A: Calicheamicins are DNA cleaving agents. They bind with DNA in the minor groove in a relatively sequence-specific manner. Once bound, they cause strand scission, which leads to cell death. They are structurally distinct from tubulin inhibitors like auristatins.
What type of linker connects the antibody and toxin?

A: This product utilizes an acetyl butyrate linker. It is designed to facilitate the release of the calicheamicin payload. The specific chemistry allows for the targeted delivery of the DNA-damaging agent to CD33-positive cells, such as those found in AML.

View the frequently asked questions answered by Creative Biolabs Support.

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Downloadable Resources

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Datasheet

Datasheet - ADC-L025.pdf

MSDS

MSDS - ADC-L025.pdf

COA

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