# Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys

Source: https://onco.cc/key-papers/paper-cardillo-clin-cancer-res/  
OnCo record `paper-cardillo-clin-cancer-res` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Paper cited by one term page, indexed on Europe PMC as PubMed record 21372224 and published in Clinical Cancer Research; the citing page links this DOI, which is how the record was matched.

## Summary

Purpose: Evaluate the efficacy of an SN-38-anti-Trop-2 antibody-drug conjugate (ADC) against several human solid tumor types, and to assess its tolerability in mice and monkeys, the latter with tissue cross-reactivity to hRS7 similar to humans.

Experimental design: Two SN-38 derivatives, CL2-SN-38 and CL2A-SN-38, were conjugated to the anti-Trop-2-humanized antibody, hRS7. The immunoconjugates were characterized in vitro for stability, binding, and cytotoxicity. Efficacy was tested in five different human solid tumor-xenograft models that expressed Trop-2 antigen. Toxicity was assessed in mice and in Cynomolgus monkeys.

Results: The hRS7 conjugates of the two SN-38 derivatives were equivalent in drug substitution (∼ 6), cell binding (K(d) ∼ 1.2 nmol/L), cytotoxicity (IC(50) ∼ 2.2 nmol/L), and serum stability in vitro (t/(½) ∼ 20 hours). Exposure of cells to the ADC demonstrated signaling pathways leading to PARP cleavage, but differences versus free SN-38 in p53 and p21 upregulation were noted. Significant antitumor effects were produced by hRS7-SN-38 at nontoxic doses in mice bearing Calu-3 (P ≤ 0.05), Capan-1 (P < 0.018), BxPC-3 (P < 0.005), and COLO 205 tumors (P < 0.033) when compared to nontargeting control ADCs. Mice tolerated a dose of 2 × 12 mg/kg (SN-38 equivalents) with only short-lived elevations in ALT and AST liver enzyme levels. Cynomolgus monkeys infused with 2 × 0.96 mg/kg exhibited only transient decreases in blood counts, although, importantly, the values did not fall below normal ranges.

Conclusions: The anti-Trop-2 hRS7-CL2A-SN-38 ADC provides significant and specific antitumor effects against a range of human solid tumor types. It is well tolerated in monkeys, with tissue Trop-2 expression similar to humans, at clinically relevant doses, and warrants clinical investigation.

Indexed on Europe PMC as PubMed record 21372224 (DOI 10.1158/1078-0432.ccr-10-2939). Matched by DOI alone: one term page cites this DOI among its external links (the pages are listed under Related), and this page was written so that the citation resolves inside OnCo. No figure has been checked by an editor.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Tags: europepmc-ingest
- Journal: Clinical Cancer Research
- Year: 2011
- DOI: 10.1158/1078-0432.ccr-10-2939
- Authors: Cardillo TM, Govindan SV, Sharkey RM, et al.
- What it means: One term page on OnCo cites this paper by its DOI; this record gives the citation a page of its own so a reader can follow it without leaving OnCo. Read the abstract above alongside the citing page listed under Related; the record was created automatically from the Europe PMC entry and its figures have not been checked by hand.
- Caveats: Matched to the citing OnCo records by DOI alone; the summary reproduces the Europe PMC abstract and no figure has been verified against the full paper.

## Sources

- Clin Cancer Res 2011: https://doi.org/10.1158/1078-0432.ccr-10-2939
- PubMed: https://pubmed.ncbi.nlm.nih.gov/21372224/
- Europe PMC: https://europepmc.org/article/MED/21372224

## Connected records

- terms: [CL2A](https://onco.cc/terms/cl2a/)
- journals: [Clinical Cancer Research](https://onco.cc/journals/clinical-cancer-research/)

---
JSON: https://onco.cc/api/v1/entities/paper-cardillo-clin-cancer-res.json