Antibody-Immunostimulant Conjugates

Antibody-immunostimulant conjugates link powerful immune-stimulating payloads, such as toll-like receptor (TLR) agonists, stimulator of interferon gene (STING) agonists, and chemokines, to tumor-targeting mAbs and are systemically delivered. This novel therapeutic has demonstrated tumor eradication in preclinical models and activation of the innate immune system to generate an adaptive immune response which leads to durable T cell-mediated tumor clearance and surveillance. Creative Biolabs’ considerable experience in dendritic cell biology and insight into the human immune system led to the discovery of the antibody-immunostimulant conjugates.

The Overview of Antibody-Immunostimulant Conjugates

Immune-based therapy has been added as a major and widely used component of cancer therapy. The overlap of ADC technology with immunotherapy comes from the addition of immunostimulant payloads such as TLR agonists, STING agonists, and chemokines to ADCs. Many immunostimulants cannot be safely administered systemically, but by using a specific targeting antibody, they can be delivered to either antigen on the tumor cell or antigen on stromal cells in the tumor microenvironment (TME). This strategy to turn tumors that are considered immunologically “cold” into “hot” may be viable using antibody-immunostimulant conjugates in a field where either systemic administration or intratumoral injections have been disappointing.

Fig.1 The process of antibody-immunostimulant conjugates exerting activity. (Comeau, 2020)

As mentioned previously, defined innate immune mechanisms involving cancer therapy include, but are not limited to antitumor immune responses elicited by recognition of tumor-derived antigens by TLRs, as well as the sensation of tumor-derived DNA by the STING. The crucial regulators of these innate antitumor immune mechanisms have attracted increasing attention as therapeutic targets.

Antibody-Immunostimulant Conjugates Development Service

A deeper knowledge of these therapeutically relevant targets in TLRs, STING, and chemokines-mediated innate immune pathways is leading toward novel antibody-immunostimulant conjugates for cancer treatment. At Creative Biolabs, we can offer the following antibody-immunostimulant conjugates development services:

• Antibody-TLR Agonist Conjugates

The TLR agonists have been actively pursuing their antitumor potentials, either as monotherapy or as adjuvants to vaccination or other therapeutic modalities. TLR agonists used as single agents especially when applied locally can effectively eradicate tumors due to their potent stimulation of innate and adaptive immunity as well as their effects on the tumor microenvironment. TLR agonists also represent promising vaccine adjuvants as they are potent DC activators, augment T-cell responses, and downregulate suppressive effects of Tregs.

• Antibody-STING Agonist Conjugates

A number of natural and synthetic STING agonists have been discovered or developed and tested in preclinical models and the clinic for the immunotherapy of diseases such as cancer and infectious diseases. Cyclic dinucleotides (CDNs), such as cyclic dimeric guanosine monophosphate (c-di-GMP), cyclic dimeric adenosine monophosphate (c-di-AMP), and cyclic GMP-AMP (cGAMP), are a class of STING agonists that can elicit immune responses.

• Antibody-Chemokines Conjugates

Chemokines play a dual role in tumor formation. They perform a useful function as an adjuvant by recruiting the immune cells to the tumor site. On the other hand, they are involved in tumor survival, metastasis, and neovascularization. Chemokine can function as growth and/or survival factor for certain cancer cell types. In antibody-chemokine fusion strategy, tumor-specific antibody part targets the chemokine into the tumor, thereby facilitating the intratumoral infiltration of immune cells.

Creative Biolabs has been involved in the development of antibody-drug conjugates for many years. Based on advanced platforms and rich expertise in antibody production and bioconjugation, we can provide you with the best services to ensure your requirements are met. If you are interested in our antibody-immunostimulant conjugate development services, please contact us for more details.

Reference

1. Comeau, M. R., et al. SBT6050, a HER2-directed TLR8 ImmunoTAC™ therapeutic, is a potent human myeloid cell agonist that provides opportunity for single agent clinical activity. 2020, 4537-4537.

For Research Use Only. NOT FOR CLINICAL USE.