Illustration of Immune Cells Destroying Tumor

Unlocking New Cancer Weapons: Antibodies That Home In on Tumors

Rhea Morgan in Science & Nature September 2025 • 4 min read.

"Innovative antibody research identifies tumor-selective antigens, offering hope for targeted cancer treatments from immunotherapy"

Anti-tumor therapy with antibody-drug conjugates (ADCs) is based on antibodies that demonstrate suitable selectivity for tumor cells, as well as internalization upon binding their cognate target. Remarkably, only a select number of such antibodies with the propensity to internalize have been identified, limiting the range and breadth of ADC therapeutics in the clinic.

Atreca's Immune Repertoire Capture (IRC) technology identifies potent anti-tumor antibodies with internalization activity applicable for ADC therapeutics from patients undergoing immunotherapy. Patient-derived antibodies from several cancer types bound to human tumor tissue but not adjacent normal tissue and also internalized into A549 lung tumor cells.

These internalizing antibodies were able to induce target cell death in vitro when conjugated directly or indirectly to a cytotoxic agent across several human tumor cell lines. Atreca's IRC technology can identify potent anti-tumor antibodies with internalization activity applicable for ADC therapeutics from patients undergoing immunotherapy.

Patient-Derived Antibodies

Illustration of Immune Cells Destroying Tumor

Patient-derived antibodies, sourced from diverse cancer types, exhibit a targeted affinity for human tumor tissue while sparing adjacent normal tissue. Notably, these antibodies demonstrate a remarkable ability to internalize within A549 lung tumor cells, indicating their potential as effective vehicles for targeted drug delivery. These internalizing antibodies exhibit the capacity to induce target cell death in vitro when conjugated, whether directly or indirectly, to a cytotoxic agent across multiple human tumor cell lines.

Atreca's IRC technology enables the identification of patient-derived antibodies with specificity for tumor-selective antigens, displaying internalization activity suitable for antibody-drug conjugate (ADC) therapeutics sourced from patients undergoing immunotherapy. These antibodies, characterized by high internalization rates, were conjugated with auristatin MMAE and tested in an in vitro ADC assay.

Briefly, plasmablasts were collected from patients and paired heavy and light chain antibody sequences were then obtained from individual cells. Antibody sequences representing expanded clonal families were subsequently expressed and analyzed for their ability to bind to human tumor and non-tumor tissues. Antibodies with a high internalization rate were directly conjugated with a cytotoxic agent (auristatin MMAE) and tested in an in vitro ADC assay.

Patient-derived antibodies from several cancer types bound to human tumor tissue but not adjacent normal tissue and also internalized into A549 lung tumor cells. These internalizing antibodies were able to induce target cell death in vitro when conjugated directly or indirectly to a cytotoxic agent across several human tumor cell lines.

The Horizon of Possibilities

This study reveals that Atreca's Immune Repertoire Capture (IRCm) technology can identify potent anti-tumor antibodies with internalization activity applicable for ADC therapeutics from patients undergoing immunotherapy. These antibodies can deliver a cytotoxic payload to target tumor cells to induce cell death, suggesting that Atreca's technology can improve ADC therapeutics.

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Everything You Need To Know

What are antibody-drug conjugates (ADCs) and how do they work in the context of cancer treatment?

Antibody-drug conjugates (ADCs) are a type of anti-tumor therapy that uses antibodies to target and deliver cytotoxic agents directly to cancer cells. The antibodies, which must demonstrate suitable selectivity for tumor cells, bind to specific targets on the tumor cells. This binding triggers the internalization of the ADC into the cancer cell. Once inside, the cytotoxic agent is released, leading to cell death. The article highlights that Atreca's Immune Repertoire Capture (IRC) technology identifies antibodies with internalization activity applicable for ADC therapeutics.

How does Atreca's Immune Repertoire Capture (IRC) technology contribute to the development of ADC therapies?

Atreca's Immune Repertoire Capture (IRC) technology plays a crucial role in identifying potent anti-tumor antibodies with internalization activity. This technology is used to analyze patient-derived antibodies, sourced from patients undergoing immunotherapy. The IRC technology allows researchers to find antibodies that specifically bind to human tumor tissue but not to adjacent normal tissue. These antibodies are then tested for their ability to internalize into tumor cells and induce target cell death when conjugated to a cytotoxic agent, like auristatin MMAE. This process enhances the range and breadth of ADC therapeutics available.

What is the significance of patient-derived antibodies in targeted cancer treatments?

Patient-derived antibodies are significant because they are sourced directly from patients and can be highly specific to the individual's cancer cells. These antibodies exhibit a targeted affinity for human tumor tissue while sparing adjacent normal tissue. The article shows that these antibodies can also internalize within A549 lung tumor cells, which indicates their potential for targeted drug delivery. This specificity minimizes damage to healthy cells, thereby reducing side effects and improving treatment efficacy. These antibodies are identified through technologies such as Atreca's IRC.

Can you explain the process of how Atreca's IRC technology identifies and utilizes antibodies for ADC therapies?

First, plasmablasts are collected from patients, and paired heavy and light chain antibody sequences are obtained. These sequences represent expanded clonal families are then expressed and analyzed for their ability to bind to human tumor and non-tumor tissues. The antibodies with high internalization rates are selected. Those antibodies are directly conjugated with a cytotoxic agent, such as auristatin MMAE, and tested in an in vitro ADC assay. This process allows the identification of antibodies that specifically target tumor cells and internalize into them, making them suitable for ADC therapies.

What are the implications of using antibodies with high internalization rates in ADC therapies?

Antibodies with high internalization rates are critical for the effectiveness of ADC therapies. Internalization ensures that the cytotoxic agent is delivered directly into the cancer cell, maximizing its impact and reducing exposure to healthy cells. This process is further enhanced when the antibody targets a tumor-selective antigen, ensuring that the drug is delivered to the intended cells. The high internalization rate contributes to the ability of the ADC to induce target cell death in vitro across multiple human tumor cell lines, as demonstrated using antibodies identified by Atreca's IRC technology.