Evaluation of ADCs in PDX Tumor Models at EPO-Berlin

EPO’s PDX models have been used in several recent developments in ADC research, including validating the efficacy and tolerability of Oncofetal Chondroitin Sulfate (ofCS)-targeting antibody fragments as ADCs in Pancreatic Ductal Adenocarcinoma (PDAC).

Studies in our IL3RA-positive AML11655 model, treated with IL3RA-targeting ADCs, demonstrated improved survival and reduced tumor burden.

Our models have also validated the efficacy of Mesothelin targeting ADCs in Ovarian Cancer and Mesothelioma, and of C4.4A-targeting ADCs in on-Small Cell Lung Cancer (NSCLC), highlighting the success of ADCs in treating Squamous Cell Carcinoma (SCC) subtypes.

Experiments in CAIX-targeting ADCs revealed selective shrinkage in our CAIX-Overexpressing PDX models, particularly within SCC subtypes.

Elucidating Combination Therapy in ADCs

Studies in our PDX models have demonstrated enhanced efficacy in ADCs when combined with Standard-of-Care (SoC) chemotherapy, revealing key insights into ADC Targeting and Internalization.

Developing SMDCs for Treatment of Triple-Negative Breast Cancer (TNBC)

A Study in two of our Orthotopic Metastatic TNBC models, treated with an αvβ3-targeting SMDC resulted in long-lasting tumor regression and reduced brain and lung metastases.

Similar efficacy was demonstrated in our Subcutaneous PDX models of Non-Small-Cell Lung, Colon, and Renal Cancers, highlighting the potential of SMDCs for difficult to treat metastatic cancers.

“Methodology” Spotlight on IncuCyte for in vitro ADCs

We are leveraging IncuCyte technology to generate in vitro ADC data for validation of ADC effectiveness in tumor-targeting and for providing insights into drug efficacy and resistance mechanisms.

Highlighting Recent Publications:

• Nat Commun (2024): Novel antibody fragments targeting Oncofetal Chondroitin Sulfate (ofCS) conjugated to MMAE were evaluated in PDX models of PDAC and UPS at EPO-Berlin, demonstrating robust efficacy.
  https://pubmed.ncbi.nlm.nih.gov/39215044/

• Cancers (2023): VIP236 (SMDC targeting αvβ3) designed and tested in PDX models of NSCLC, CRC, and TNBC at EPO-Berlin, demonstrating improved survival, reduced tumor burden, and significant antitumor efficacy.
  https://pubmed.ncbi.nlm.nih.gov/37686656/

• Cancers (2020): IL3RA-targeting ADCs were evaluated in PDX models of AML11655 at EPO-Berlin, demonstrating improved survival, reduced tumor burden, and significant antitumor efficacy.
  https://pubmed.ncbi.nlm.nih.gov/33233768/

• Oncotarget (2018): Mesothelin targeting ADC was evaluated in PDX models of Mesothelin-Expressing Ovarian Cancer at EPO-Berlin, demonstrating potent antitumor activity both in monotherapy, and in combo with SoC.
  https://pubmed.ncbi.nlm.nih.gov/30344925/

• Mol Cancer Ther (2017): C4.4A-targeting ADCs was evaluated at EPO-Berlin in two human CDX and four PDX models of NSCLC models in vivo, highlighting its efficacy in squamous cell carcinoma.
  https://pubmed.ncbi.nlm.nih.gov/28292941/

• Mol Cancer Ther (2014): Mesothelin-targeting ADC (MF-T conjugated to DM4) evaluated in PDX models of Mesothelin-Expressing Cancers (Mesothelioma, Ovarian) at EPO-Berlin, demonstrating high selectivity and antitumor efficacy.
  https://pubmed.ncbi.nlm.nih.gov/24714131/

• Molecular Cancer Therapeutics (2012): CAIX-targeting ADC (mAb 3ee9 conjugated to MMAE) demonstrate potent antitumor efficacy across multiple PDX CAIX-Overexpressing Solid Tumor models in studies at EPO-Berlin.
  https://pubmed.ncbi.nlm.nih.gov/22147747/

Our colleague Turn on Javascript! is attending this year’s ADC Conference in San Diego (Nov 4–7) and will also be in San Francisco (Nov 7–8); reach out to arrange an in-person meeting or video call with him.

For more information, contact Turn on Javascript! and Turn on Javascript!%3e" target="_blank">Prof. Wolfgang Walther to discuss how we can accelerate development of your therapeutic ADC.

Best regards,
Jens Hoffmann & Wolfgang Walther
CEO & CSO at EPO Berlin-Buch