The ABCs of ADCs: An Introduction to Antibody-drug Conjugates

The terms “warhead” and “payload” typically invoke impressions of weapons and destruction. However, in a more constructive and positive light, these terms are now also commonly associated with antibody-drug conjugates (ADCs), a class of biologics used to treat cancer. These warheads and cytotoxic payloads are an integral part of ADCs that drive tumor cell death. Coupled to antibodies, ADCs combine the advantage of both modalities to be a potent class of anti-cancer molecules.In this blog, we will discuss the components that make up ADCs, what they are used for, and the future for this class of biologics. What [...]

By |2021-06-29T22:06:32-08:00June 18th, 2021|Antibody-drug Conjugates, Bioservices, Blog|0 Comments

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 [...]

T’ing it Up for Bi-Specific Antibodies…(Part 2)

In our previous blog, we discussed the two-predominant types of T cells, and some in vitro assays these cells are employed in to test the function and specificity of bi-specific antibodies.  In this blog, we discuss the in vivo assays that test the efficacy of these antibodies and tie it all together by reviewing some data generated with these assays. What are some T cell-based in vivo assays used to examine bi-specific antibody efficacy? Most preclinical in vivo experiments that examine the efficacy of bi-specific antibodies are performed using immuno-deficient mice, such as the NOD scid gamma (NSG) mice.  These mice [...]

By |2018-06-05T01:24:16-08:00January 9th, 2018|Bi-specific Antibody, Blog, T Cells|0 Comments

T’ing it Up for Bi-Specific Antibodies…(Part 1)

With the current trend of developing immunotherapies for cancer, many of these therapies center on exploiting the potent effector functions of lymphocytes, specifically T cells.  In our previous blogs, we introduced a new class of therapeutic molecules called bi-specific antibodies and discussed their mechanism of action for anti-cancer therapy.  In this blog, we will discuss in vitro assays that use T cells to develop bi-specific antibody programs. What are CD4 and CD8 T cells? In most organismal immune systems, there are two main types of T cells.  One type is the CD4 T cell, which is a hematopoietic cell that [...]

By |2018-05-30T01:26:01-08:00November 7th, 2017|Bi-specific Antibody, Blog, T Cells|0 Comments

Antibodies with a Split Personality…(Part 3)

In the final part of our series on bi-specific antibodies, we’ll discuss some of the assays that are used to test the specificity, functionality, and safety of bi-specific antibodies. How are bi-specific antibodies tested for antigen specificity? As described in our previous blogs, bi-specific antibodies have the capability to recognize two different antigens due to the presence of two different antigen recognition domains.  To ensure that each arm has specificity for the correct antigen, binding assays are performed with a cell line that expresses the antigen recognized by one arm of the bi-specific antibody.  Typically, flow cytometry is used as [...]

By |2018-05-30T01:26:01-08:00August 8th, 2017|Bi-specific Antibody, Blog|0 Comments

Antibodies with a Split Personality…(Part 2)

How were bi-specific antibodies initially created? Each individual bivalent, monospecific antibody is composed of two identical heavy chains and two identical light chains, in which a single heavy chain combines with a light chain to create an individual target antigen recognition site.  Since there are two antigen binding sites per antibody, two heavy-light chain pairs combine and form a bivalent, monospecific antibody.  When producing these antibodies, only one heavy chain and its corresponding light chain is expressed by the cells because there is only one specific target antigen for the antibody. In contrast, bi-specific antibodies are created by expressing two [...]

By |2018-05-30T01:26:02-08:00June 13th, 2017|Bi-specific Antibody, Blog|0 Comments