In addition, using immunohistological staining, we found that CD70 was expressed on 10 of 10 patients who had progressed on BCMA targeted therapies (seven who had progressed on belantamab mafodotin, an antibody drug conjugate, three who had progressed on idecabtagene vicleucel, a BCMA CAR-T), suggesting that CD70 could be a viable target in patients who have failed BCMA targeted therapy. In summary, we were able to demonstrate that CD70 can be a feasible target for the treatment of multiple myeloma, including in patients who have failed BCMA targeted therapy. Based on these results, we have initiated a Phase I/II clinical trial (NCT05092451) that is currently recruiting.

PK, immunogenicity, and antitumor activity will also be evaluated. The study is currently enrolling at sites in the US, with future enrollment in China planned.

Conclusions In summary, the highly selective and potent anti-tumor activity in multiple tumor types and wide pre-clinical therapeutic index of ARX305 support clinical evaluation of this next generation anti-CD70 ADC. ARX305 is currently in a phase 1 dose-escalation study in China.

No abstract available

CXCR5 is a highly attractive target in hematological malignancies such as DLBCL, MCL, and FL due to high protein expression and almost no expression in healthy tissues. CXCR5-targeting ADC with KSPi payload showed high potency and superiority to other B-cell-targeted ADCs in vitro on a broad range of lymphoma cell lines. VIP924 with a novel legumain-cleavable linker showed activity in in vivo PDX models from lymphoma patients.

In summary, the highly potent anti-tumor activity in multiple tumor types and wide therapeutic index of ARX305 support clinical evaluation of this next generation anti-CD70 ADC. ARX305 is currently in a Phase 1 dose escalation study in China, and the IND in the United States is open.

Anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting chimeric antigen receptor (CAR) T cell and CAR NK cells show potent activity against EGFR TKI-resistant cells and DTPCs. These results identify CD70 as a therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits clinical investigation.

Although these patients are initially highly sensitive to first or second generation EGFR tyrosine kinase inhibitors (TKIs) including erlotinib or third-generation inhibitors including osimertinib, EGFR TKI-refractory disease inevitably emerges. CD70-targeting approaches including anti-CD70 antibody drug conjugates (ADCs) and CD70-targeting CAR T cell and CAR NK cells showed promising in vitro and in vivo activity against CD70 positive tumor cells and in osimertinib drug-tolerant persister cells. These results identify CD70 as a novel therapeutic target for EGFR mutant tumors with acquired EGFR TKI resistance that merits further investigation in the clinic.

PRO1160 has the potential for an expanded therapeutic index. PRO1160 is being developed for the potential treatment of patients with CD70-expressing hematologic and solid tumor cancers.

Gemtuzumab ozogamicin, a CD33-directed antibody-drug conjugate, is the only Food and Drug Administration-approved monoclonal antibody (mAb) in AML providing evidence for the potential future role of mAb-based therapies in AML. This article provides an overview of the progress made in targeted immunotherapy in AML, particularly focusing on unconjugated and conjugated mAbs.

Most importantly, multiple-dosing of SGN-CD70A induced complete eradication of established tumors in PDXs measured by cfDNA. Our results demonstrated marked anti-tumor activity of SGN-CD70A in CTCL PDXs, providing compelling support for its clinical investigation.

AXL was expressed especially in MFS and STLMS. Sarcoma subtypes express multiple target genes relevant for ADCs, SPEAR T-cells and CAR's, warranting further clinical validation and evaluation.

Western blotting and fluorescence-activated cell sorting analyses were used to determine CD70 expression in the ovarian cancer cell lines, A2780 and SKOV3, and in the cisplatin-resistant ovarian cancer cell lines, A2780cisR and SKOV3cisR...Platinum treatment induced CD70 expression in ovarian cancer cells. CD70-ADC may have potential therapeutic implications in the treatment of CD70 expressing ovarian cancer.

One week after tumor inoculation, mice were treated intraperitoneally with single-dosing of PBS, 100 μg/kg (SGN70A100) or 300 μg/kg (SGN70A300) of SGN-CD70A. Using CTCL PDX models, SGN-CD70A has marked anti-tumor activity, leading to long-term survival of treated mice. Our results provide a rationale for clinical investigation of SGN-CD70A in patients with TCL.

Gemtuzumab ozogamicin, a CD33 directed antibody-drug conjugate, has provided the proof of concept for the potential efficacy of monoclonal antibody-based therapies in AML...The first-in-class anti-CD47 antibody magrolimab and anti-CD70 antibody cusatuzumab in combination with hypomethylating agent (HMA) azacitidine, in newly diagnosed AML, and flotetuzumab, a bispecific DART® (dual-affinity retargeting) antibody to CD3ε and CD123 as salvage option in relapsed/refractory AML appear promising...Ongoing research will define the choice of an appropriate complementary therapeutic agent in antibody-based combination therapy, and whether one or more than one antigen should be simultaneously targeted. Further studies will likely refine the role of antibody-based therapy in post hematopoietic cell transplant setting.

Uterine leiomyosarcoma tumors highly express CD70 and targeted therapy with CD70-ADC may have a potential therapeutic implication in the treatment of uterine leiomyosarcoma.

The anti-CD70 ADC offers some chemotherapeutic potential for the treatment of ATL.