ADCP: The Covert MoA for Therapeutic Antibodies You Need to Know About (Part 2)

In our previous blog, we discussed antibody-dependent cellular phagocytosis (ADCP), a mechanism of action for therapeutic antibodies that is becoming increasingly appreciated. In vitro and in vivo experiments show that ADCP, a process where phagocytic cells ingest and lyse opsonized target cells, can clear lymphoma cells in the presence of therapeutic antibodies.  To harness the potential of these antibodies, researchers have sought to determine the factors that influence ADCP. What are 3 currently known factors that can impact ADCP? Phagocytic Effector Cell Subtype - Like mentioned above, ADCP is performed by phagocytic cell types that include monocytes, macrophages, [...]

ADCP: The Covert MoA for Therapeutic Antibodies You Need to Know About (Part 1)

Therapeutic antibodies can work through various mechanisms of action.  They can inhibit ligand-independent dimerization to prevent downstream survival and proliferation signaling pathways or induce apoptosis of target cells.  In addition, therapeutic antibodies can activate the immune system to drive antibody-dependent cellular cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) to eliminate aberrant cells.  However, one lesser known mechanism mediated by the immune system that is also driven by these antibodies is antibody-dependent cellular phagocytosis (ADCP). In this blog, we will introduce ADCP and discuss the data that supports its role in the anti-tumoral effects of therapeutic antibodies. What is antibody-dependent [...]

Revisiting Complement, An Old Friend… (Part 3)

After summarizing how the complement system can have both anti-tumor and pro-tumor effects, we conclude our blog series on Reis et al. by discussing the clinical aspects of complement as a target and biomarker.  As discussed in the previous blogs, the imbalance in activation of complement leads to overproduction of complement proteins that causes a switch from immunosurveillance to tumorigenesis.  Thus, therapeutics may be developed that target complement proteins and fragments to restore balance and an effective immune environment. Using complement to enhance monoclonal antibody-based (mAb) therapies Engineering antibodies to enhance Fc region-mediated effector functions have been well [...]

Revisiting Complement, An Old Friend… (Part 2)

Complement in promotion of tumorigenesis. The imbalance and dysfunction of complement activity and activation can lead to various mechanisms that promote tumorigenesis. These mechanisms can have affects on the immune cells to provide a more favorable tumor growth environment, including: 1) recruitment of MDSCs, 2) suppression of effector T cell function, and 3) sustained release of pro-inflammatory factors for favorable tumor growth. In addition, loss of complement regulation has affects on non-immune cells that sustain tumor growth and metastasis, including: 1) angiogenesis, 2) abnormal tumor cell proliferation, and 3) cell invasion and metastasis. Please see our blogs for more [...]

Revisiting Complement, An Old Friend… (Part 1)

The complement system of the innate immune system has been widely regarded as an early deterrent to infections and a means to clear pathogens by activating a group of proteins that leads to cell lysis, phagocytosis, and inflammation.  In addition, the power of complement has been implicated as a mechanism by which therapeutic antibodies, such as Rituxan, promoted their anti-tumor effects.  Along those lines, many biotechnology and pharmaceutical companies have tried to harness that power in targeted monoclonal antibody (mAb) cancer therapies.  However, more recent findings have indicated that, like everything about the immune system, balance is key and dysregulation [...]

Serious Monkey Business: A Short Take on Cynomolgus Monkeys in Research

What are cynomolgus monkeys? Cynomolgus monkeys (Macaca fascicularis), also known as the long-tailed or crab-eating macaque, are non-human primates (NHP) commonly used in biomedical research.  There are 10 subspecies of these macaques and they are found predominantly in southeast Asia.  The cynomolgus monkeys are typically 15-22 inches long, and the females weigh between 7-13 pounds, while males can weigh between 11-20 pounds. Why use cynomolgus monkeys and how are they used in biomedical research? Cynomolgus monkeys are frequently used in biomedical research because researchers believe these monkeys are the ideal models due to the 90-93% genetic similarity to and recent [...]

Hurry up and Wait? The recent fuss about CAR-Ts

What are CAR-T cells? CAR (chimeric antigen receptor) T cells (CAR-T) are genetically engineered T cells that express receptors which recognize cancer antigens and attack the cells that express them. Therefore, they are a new cell-based immunotherapy for oncology indications. The results for leukemia and lymphoma patients receiving CD19-specific CAR-T cells have been extremely promising so far. CAR-T currently come in two main flavors: autologous or allogeneic. In order to prevent an allogeneic response against foreign T cells, CAR T cells are generated from the patient’s own T cells. T cells are taken from the patient and genetically engineered to [...]

Immuno-Oncology: I-O, I-O, Off to Fighting Cancer We Go… (Part 3)

What assays are used to identify good therapeutic candidates that modulate the immune response? This is Part 3 of our series, “Immuno-Oncology: I-O, I-O, Off to Fighting Cancer We Go…”. Miss Part 1 or Part 2? Catch up! What assays are used to identify good therapeutic candidates that modulate the immune response? The approval of Yervoy ushered in a new era of cancer treatment options where the immune system could be modulated to attack and eliminate cancer cells. Following suit, it is forecasted by financial experts that the immuno-oncology treatment space could be worth $20-50 billion dollars by 2020. Not [...]

By |2018-05-30T01:26:10+00:00July 5th, 2016|Bioservices, Blog, Immuno-Oncology|0 Comments

Immuno-Oncology: I-O, I-O, Off to Fighting Cancer We Go… (Part 2)

What molecules can modulate the immune response? What are examples of those being developed as therapeutics? This is Part 2 of our series, “Immuno-Oncology: I-O, I-O, Off to Fighting Cancer We Go…”. Miss Part 1? Catch up here. What are some of the molecules that inhibit immune response currently being developed? As mentioned in Part 1, therapeutics against checkpoint inhibitor molecules, such as CTLA-4 and PD-1, are currently approved for certain indications while also undergoing clinical trials for others. In addition, trials are underway for therapeutics that target PD-L1, the ligand for PD-1, which is found to be up-regulated in [...]

By |2018-05-30T01:26:10+00:00June 7th, 2016|Bioservices, Blog, Immuno-Oncology|0 Comments

Immuno-Oncology: I-O, I-O, Off to Fighting Cancer We Go… (Part 1)

What is I-O? What are checkpoint inhibitors? What is immuno-oncology? The field of immuno-oncology, also known as cancer immunotherapy, is centered on mobilizing the immune system to attack cancer cells and eradicate tumors. With this approach, therapeutics target molecules on lymphocytes that will either activate them or keep them from being inactivated, in order to sustain the immune response. With a sustained response, the immune system can search for and eliminate cancerous cells and tumors. Many years of research and development went into targeting these types of molecules on lymphocytes and, finally, with the approval of Yervoy® (ipilimumab, by [...]

By |2018-05-30T01:26:11+00:00May 10th, 2016|Bioservices, Blog, Immuno-Oncology|0 Comments