ADC Development for Prostate Cancer

Prostate cancer is one of the most common cancers in men. The standard treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) have been assessed but failed to improve the overall survival (OS). Currently, novel treatment methods such as the targeted antibody-drug conjugates (ADCs) have been found to significantly improve the progression-free survival and OS rates.

Creative Biolabs offers high-quality services in the ADCs discovery and development against mutiple cancers. With a lot of talent scientists and technicians, we have built excellent and mature platforms for the development and manufacturing of ADCs. In addition, we will also save your time and cost by taking advantage of our expertise and innovative bio-conjugation and analysis technology.

Introduction of Prostate Cancer

Prostate cancer is cancer that arises in the prostate, a small walnut-shaped gland in the male reproductive system to produce the seminal fluid. In general, most prostate cancer grows slowly and limitedly in the prostate gland. While some of the cancer are aggressive and can spread quickly to other organs especially the bones and lymph nodes. Symptoms during the cancer mainly show difficulty urinating, decreased force in the stream of urine, blood in semen, discomfort in the pelvic area, bone pain and erectile dysfunction. Although the specific cause of prostate is unclear, some risk factors may include age, race, family history and obesity. Besides, the cancer often leads to some complications such as the metastasis and incontinence. The treatment options for this cancer include surgery to remove the prostate, radiation therapy, hormone therapy, chemotherapy and biological therapy.

Metastatic properties of prostate cancer. Fig.1 Metastatic properties of prostate cancer. (Perera, 2016)

Current Therapeutic Strategies for Prostate Cancer

Currently, prostate cancer has a high incidence in the male and leads to a large number of cancer-related deaths, despite the diagnostic and therapeutic advances. Some novel therapeutic agents have improved the outcome of the cancer. Some approval drugs have potent anti-tumor efficacy in treatment-resistant prostate cancer patients, such as the abiraterone acetate, enzalutamide and apalutamide targeting the androgen signaling. AKT inhibitor target PI3K/AKT/mTOR pathway such as the ipatasertib is assessed in clinical phase 3 for mCRPC patients currently, which is showing promising and successful. Besides, Fibroblast growth factor (FGF) signaling also plays an important role in prostate cancer. AZD4547 and Dovitinib are FGF inhibitors which have been investigated in clinical studies. Olaparib is a poly ADP ribose polymerase (PARP) inhibitor against the DNA damage repair pathway showing significant improvement in advanced prostate cancer.

Targeted alpha therapy approach is also a new treatment method in prostate cancer, such as the Radium-223 dichloride that significantly improves the overall survival of CRPC patients. Besides, radium-223 dichloride can induce T cell-mediated lysis in prostate cancer as a kind of immunotherapy and may have additional clinical benefit. Prostate-specific membrane antigen (PSMA) targeting approach is another novel immunotherapy. Specific ADCs targeting PSMA such as the PSMA ADC, MLN2704 and MEDI3726 (ADC-401) have been developed, which have shown strong efficacy and high response variability in preclinical and clinical trials in prostate cancer.

Structures of PSMA ADC. Fig.2 Structures of PSMA ADC. (Wang, 2011)

Other immunotherapy strategies such as the Sipuleucel-T has been approved in 2010 for mCRPC therapy. This method presents long-term clinical benefits and manageable side-effects. Immune checkpoint inhibitors such as the anti-CTLA4 antibody ipilimumab and anti-PD-1 antibody pembrolizumab have shown some promising results in prostate cancer.

What Can We Do for You?

Scientists at Creative Biolabs are experts in antibody/protein development and antibody/protein-drug conjugation. At present, we provide a full range of ADCs design and construction services against prostate cancer. Our best-quality services include specific antibody development, potent drug or linker-payload production and effective bio-conjugation with unbeatable rapid turnaround times. Targets of ADC development for prostate cancer:

For more detailed information, please feel free to contact us or directly sent us an inquiry.

References

  1. Perera, M.; et al. An update on focal therapy for prostate cancer. Nature Reviews Urology. 2016.
  2. Wang, X.; et al. In vitro and in vivo responses of advanced prostate tumors to PSMA ADC, an auristatin-conjugated antibody to prostate-specific membrane antigen. Molecular cancer therapeutics. 2011, 10(9): 1728-1739.


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