ADC Development for Colorectal Cancer (CRC)

Colorectal cancer (CRC) is a common cancer. Traditional treatments for this cancer often cause tumor relapse, metastasis and therapeutic resistance. Antibody-drug conjugates (ADCs) representing a novel class of therapeutic agents that combine the potency of potent toxic small molecule drugs with the targeting capabilities of highly-specific antibodies, are showing unique advantages in the CRC treatment. At Creative Biolabs, end-to-end ADCs design and construction services allow for multiple entry points for clients, starting from the development of a specific monoclonal antibody and ADC to in vivo safety and efficacy validation.

Introduction of CRC

CRC is a kind of cancer arising from the colon or rectum, which is characterized by the abnormal cells growth out of control to invade or spread to other organs or tissues of body. Common symptoms of CRC include changes in bowel habits, diarrhea or constipation, blood in feces, bright red blood in the rectum, pain and bloating in the abdomen, fatigue or tiredness and abnormal weight loss. Generally, most CRC cases are due to old age and lifestyle factors, other risk factors including genetic disorders, diet, high alcohol consumption, overweight and obesity, smoking and a lack of physical activity. Treatments for this cancer include chemotherapy, radiotherapy, and surgery, which will depend on the size, location, and stage of the cancer, recurrent or not, and the health condition of patients to perform different treatment strategies.

Different stages of CRC. Fig.1 Different stages of CRC.

ADC Development for CRC

ADC is composed of a cytotoxic drug linked to an antibody, which is specific targeted treatment approach during the cancer therapies. To date, several ADCs has been developed to target the CRC. For instance, SAR408701 (SAR) is an ADC comprising an anti-CEACAM5 antibody conjugated to a microtubule-targeting mitosis inhibitor, DM4, with a cleavable N-succinimidyl 4-(2-pyridyldithio) pentanoate linker. Pre-clinical studies demonstrated that SAR408701 has promising anti-tumour efficacy in colorectal cancer. Besides, SAR408701 also presented an acceptable safety profile during a phase I safety and pharmacokinetics study in patients with CRC.

SAR408701: an anti-CEACAM5 ADC with a cleavable linker. Fig.2 SAR408701: an anti-CEACAM5 ADC with a cleavable linker.

AbGn-107 is an ADC composed of an anti-CD71 (Transferrin receptor protein 1) antibody linked to a potent cleavable linker-tubulin inhibitor. This ADC has been studied in colorectal stomach, pancreatic, and cancers. In pre-clinical trials, AbGn-107 showed a superior antitumor efficacy in at least four xenograft tumor models. In addition, this novel ADC agent displayed significant safe and well-tolerable in non-human primates (NHP) toxicity studies.

In addition, anti-LGR5 antibody was conjugated to two potent toxic drug monomethyl auristatin E (MMAE) and PNU159682 producing two novel anti-LGR5 specific ADCs, named anti-LGR5-MC-vc-PAB-MMAE (anti-LGR5-vc-MMAE) and anti-LGR5-NMS818, respectively. Preclinical trial in targeting LGR5 positive cancer cells and animal models with colorectal cancer showed that the two ADCs have potential therapeutic efficacy. All positive results indicated that these ADCs could be investigated in further clinical trials.

What Can We Do for You?

Creative Biolabs has rich experiences in antibody production and ADC development. At present, we provide a full range of ADCs development services against the CRC for customers all over the world.Targets of our ADC development for CRC include:

CEACAM5 CD71    

Supported by proprietary cutting-edge technologies in antibody engineering, drug manufacturing and bio-conjugation platforms, Creative Biolabs is committed to provide clients top-quality ADC development and manufatcuring service. For more information, please contact us.

For Research Use Only. NOT FOR CLINICAL USE.

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