Richard Gorlick, MD, professor, department chair, Mosbacher Pediatrics Chair, Department of Pediatrics Patient Care, division head, Division of Pediatrics, director, Department of Pediatric Sarcoma Research Laboratory, The University of Texas MD Anderson Cancer Center, discusses the challenges of identifying immunotherapeutic targets in osteosarcomas.

Novel therapies are needed to treat patients with osteosarcomas, says Gorlick. Although antibody-drug conjugates have been evaluated, they have not demonstrated significant success in this disease subtype, Gorlick explains.

During the 2021 AACR Annual Meeting, results from a study showed that proteomic profiling identified multiple targets on the surface of osteosarcoma. Prior to this work, surface targets in osteosarcoma were not largely understood, Gorlick says. Some surface targets, such as HER2, that demonstrated modest expression in osteosarcoma but high expression in other cancer types were evaluated, Gorlick says. However, there doesn’t appear to be enough of the protein expressed on the surface of osteosarcoma cells to drive the effectiveness of HER2-targeted treatments, Gorlick explains. 

As such, the novel targets identified by the study may pave the way for new therapies to test in this disease subtype, concludes Gorlick.

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Richard Gorlick, MD, discusses the challenges of identifying immunotherapeutic targets in osteosarcomas.  



Dr. Gorlick on the Challenges of Identifying Immunotherapeutic Targets in Osteosarcomas 

Richard Gorlick, MD, division head of the Division of Pediatrics at The University of Texas MD Anderson Cancer Center, discusses the potential of antibody-drug conjugates (ADCs) in patients with osteosarcoma.

The ADC BT1769 is currently being examined in human clinical trials, having already gone through phase 2 clinical trials and phase 1 safety studies, Gorlick says. One of the methods that investigators utilized to identify proteins in this patient population involved examining target expression in normal tissue after identifying molecular targets that are frequently expressed in osteosarcoma. From there, investigators sought to confirm whether there was a differential expression, at a minimum, between tumor tissue and normal tissue, Gorlick says. 

Osteosarcoma is treated with standard cytotoxic chemotherapy, however, ADCs can go after cells that express a certain target, Gorlick explains. This offers an advantage over chemotherapy, as the cytotoxic adverse effects (AEs) from an ADC will not affect the whole body. Due to this, investigators theorize that even if the same agents are being utilized, the AEs will be less, Gorlick concludes.

Richard Gorlick, MD, discusses the potential of antibody-drug conjugates in patients with osteosarcoma.

Dr. Gorlick on the Potential of ADCs in Osteosarcoma

Richard Gorlick, MD, division head of the Division of Pediatrics at The University of Texas MD Anderson Cancer Center, highlights methods for identifying immunotherapeutic targets in osteosarcomas.

In a recent study, mass spectrometry was used to analyze proteins from whole protein extracts and membrane extracts from patient-derived osteosarcoma xenograft models, according to Gorlick. The research utilized human tumors that were implanted in immunocompromised mice and were permitted to grow. Investigators were able to recapitulate osteosarcomas that were obtained from patients directly, Gorlick says.

After xenograft models were analyzed comprehensively, investigators examined patient samples to confirm that the proteins expressed in the models were also expressed on the tumors that came from human patients. From there, agents could be tested on the model systems, Gorlick concludes.

Richard Gorlick, MD, highlights methods for identifying immunotherapeutic targets in osteosarcomas.

Dr. Gorlick on Methods for Identifying Immunotherapeutic Targets in Osteosarcomas

Richard Gorlick, MD, division head of the Division of Pediatrics at The University of Texas MD Anderson Cancer Center, discussed results from a study examining the use of integrative surfaceome profiling to identify immunotherapeutic targets in patients with osteosarcomas.

, results from the study showed that proteomic profiling resulted in the identification of a large number of targets on the surface of an osteosarcoma, according to Gorlick. Some of the targets had been identified previously, although this had been done intuitively through random testing, which helped to support the findings, Gorlick explains. 

Additionally, investigators presented data on an agent called BT1769 that was not previously considered for testing in osteosarcoma. The agent is only being tested in this disease because of the data yielded from this research, Gorlick notes. The agent, which was developed by Bicycle Therapeutics, targets MMP-14. Data yielded from preclinical models will be presented during the meeting. 

Importantly, investigators have identified an agent that appears to have activity in preclinical models and may help to identify future targets for this patient population, Gorlick concludes.

Richard Gorlick, MD, discussed results from a study examining the use of integrative surfaceome profiling to identify immunotherapeutic targets in patients with osteosarcomas.


Richard Gorlick, MD

Articles

Dr. Gorlick on the Challenges of Identifying Immunotherapeutic Targets in Osteosarcomas

Dr. Gorlick on the Potential of ADCs in Osteosarcoma

Dr. Gorlick on Methods for Identifying Immunotherapeutic Targets in Osteosarcomas

Dr. Gorlick on the Use of Integrative Surfaceome Profiling to Identify Targets in Osteosarcomas