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Renca Syngeneic Model Service for Renal Cancer

Fig 1: Renca Syngeneic Model for Renal Cancer preclinical research.

The Renca syngeneic model service for renal cancer is an immune-competent BALB/c platform built on the 1969 spontaneous renal cortical adenocarcinoma line whose growth pattern ATCC notes accurately mimics human adult renal cell carcinoma — particularly its spontaneous metastasis to lung and liver — across subcutaneous, orthotopic, and metastatic study formats. Alfa Cytology delivers this model as a complete preclinical capability — covering authenticated Renca / luciferase-RFP-engineered expansion and banking, intrarenal orthotopic or subcutaneous implantation with serial micro-CT and in vivo bioluminescence monitoring, and full renal histopathology with cytokeratin-8/18 tumor identification and checkpoint immunophenotyping — all configured around each sponsor’s TKI, checkpoint, combination, or vascular-targeting hypothesis.

Overview of Renca Syngeneic Model for Renal Cancer

Renca is among the oldest continuously used renal tumor lines — derived from a spontaneous renal cortical adenocarcinoma that arose in a six-week-old male BALB/cCr mouse, first described by Murphy and Hrushevsky in the Journal of the National Cancer Institute in 1973, and deposited with the ATCC by Robert Wiltrout in 1969. The ATCC’s annotation for the line remains its best one-sentence summary: its pattern of growth accurately mimics human adult renal cell carcinoma, particularly with regard to spontaneous metastasis to lung and liver. The cells are epithelial, adhere as a cobblestone monolayer, double every 24 hours, and carry two documented molecular quirks — an absent transforming growth factor-β type II receptor (which inspired a dedicated literature on receptor-reconstitution tumor suppression) and a poorly immunogenic, highly tumorigenic character that nonetheless remains susceptible to NK-cell control, as the 1985 Salup study of natural killer activity in spontaneous metastasis established. Cytokeratin 8 and 18 staining serves as the standard immunohistochemical identifier of Renca tumor cells against host background.

Fig 2: Reference figures for Renca cell-related literature.Fig 1. Longitudinal in vivo bioluminescence imaging of orthotopic Renca-luc tumors from day 7 to day 28, with ex vivo lung/kidney imaging and H&E confirming metastatic spread—the standardized imaging pipeline of the Renca orthotopic model. (Liang, Zhihuang, et al., 2026)

In vivo, the model’s versatility mirrors its history: subcutaneous grafts (5 × 106 cells) support rapid efficacy screening; intrarenal orthotopic implantation — 2 × 105 luciferase-tagged cells beneath the renal capsule — produces a primary renal mass with lung metastasis by day 24, quantifiable by kidney wet weight, India-ink lung inflation, and serial in vivo bioluminescence; and luciferase-RFP engineering enables longitudinal tracking of both sites. The therapeutic record spans the entire modern RCC era: the IL-2-stimulated cytotoxic lymphocyte work of Wiltrout in 1986 belongs to the line’s heritage; the nucleoside analog BCH-4556 — later renamed troxacitabine and advanced to phase II trials — was characterized in Renca; the vascular-disruption agent BNC105 progressed from Renca orthotopic data into a pembrolizumab-combination clinical trial; and recent combination studies provide the model’s defining quantitative signature — median survival of 28 days untreated, 34 days with cabozantinib or anti-PD-1 alone, and 49 days with their combination, with RNA-sequencing of lung metastases revealing treatment-specific pathway rewiring (FGF upregulation after monotherapy, mTOR activation after combination) that now guides sequential-therapy design. One honest caveat from CRO benchmarking deserves equal prominence: Renca subcutaneous tumors do not respond to PD-1 monotherapy, making the model an ideal setting for combinations that must outperform TKI-plus-checkpoint standards rather than a stage for single-agent checkpoint claims. Engineered derivatives — Renca-IL2, CA-IX-expressing, lacZ-tagged, and sh-PD-L1 knockdown lines — extend the platform’s reach, and PD-L1 knockdown itself sensitizes the tumors to sunitinib with increased CD8 infiltration, illustrating the immunobiology the model was built to interrogate.

Cell Line Information: Renca

The table below consolidates the key biological, cultural, and modeling characteristics of the Renca line and its engineered derivatives.

Parameter Details
Cell line designation Renca (RENCA, Renal Carcinoma); engineered derivatives include Renca-IL2, Renca/CA-IX, Renca-lacZ, Renca-GL (GFP-luciferase), Renca-Luc-RFP, and sh-PD-L1 knockdown lines
Species / genetic background Mouse (Mus musculus), BALB/cCr inbred background; syngeneic in BALB/c immunocompetent hosts
Origin Derived from a tumor that arose spontaneously as a renal cortical adenocarcinoma in a 6-week-old male BALB/cCr mouse (Murphy & Hrushevsky, Journal of the National Cancer Institute 50:1013–1025, 1973); deposited with ATCC by R. Wiltrout (1969)
Depository / catalogue ATCC CRL-2947; Cellosaurus CVCL_2174 (STR profile validated in the PLoS ONE 2019 interlaboratory mouse-cell-line study); BCRJ 0346; CLS 400321
Tumor type Murine renal cortical adenocarcinoma; ATCC notes the growth pattern accurately mimics human adult renal cell carcinoma, particularly spontaneous metastasis to lung and liver
Molecular features Does not express transforming growth factor-β type II receptor (TβRII) — receptor reconstitution confers tumor-suppressor activity (Engel et al., Urology 54:164, 1999); poorly immunogenic and highly tumorigenic; susceptible to NK-cell control of spontaneous metastases (Salup et al., Journal of Urology 134:1236, 1985); cytokeratin 8/18 positive by immunohistochemistry
Growth properties Adherent epithelial-like cells with population doubling time of approximately 24 hours; high mitotic index with anchorage-independent soft-agar colony formation
Recommended culture conditions ATCC-formulated RPMI-1640 with 10% fetal bovine serum, 0.1 mM extra non-essential amino acids, 1 mM extra sodium pyruvate, and 2 mM extra L-glutamine at 37 °C in 5% CO₂; mycoplasma not detected per ATCC quality control
Implantation formats and doses Subcutaneous: approximately 5 × 106 cells per mouse for flank efficacy studies; intrarenal orthotopic: 2 × 105 Renca-GL cells in 0.1 mL beneath the renal capsule (published model: primary renal mass and lung metastasis by day 24, quantified by kidney wet weight, India-ink lung inflation, and bioluminescence); orthotopic alternative: 1 × 106 cells in 50 μL through a 22-gauge needle into the kidney with needle retention to minimize backflow
Documented in vivo responses Median survival 28 days untreated, 34 days with cabozantinib or anti-PD-1 monotherapy, and 49 days with their combination (orthotopic model with serial micro-CT); everolimus plus anti-PD-L1 showed enhanced antitumor activity; reovirus plus sunitinib repurposing demonstrated therapeutic and tumor-specific immune responses; PD-L1 knockdown slowed flank growth and sensitized tumors to sunitinib with increased CD8⁺ infiltration; IL-2-stimulated cytotoxic lymphocytes showed adjuvant activity against established tumors (Wiltrout, Cancer Research 46:3358, 1986); BCH-4556 (troxacitabine) and BNC105 characterized in this model; PD-1 monotherapy does not control subcutaneous Renca tumors (documented CRO benchmark — a combination-model setting)
Host strains BALB/c immunocompetent mice (syngeneic); athymic nude for designated xenograft-control arms
Key research applications TKI and checkpoint-combination evaluation against the cabozantinib-plus-anti-PD-1 survival benchmark; vascular-disruption and anti-angiogenic agent screening (the BNC105 precedent); oncolytic virus plus TKI combinations; NK-cell and IL-2-era immunotherapy mechanism studies; metastasis-biology and dormancy research with luciferase-RFP tracking; CA-IX and PD-L1 engineering studies; sequential-therapy design guided by treatment-specific metastatic gene-expression signatures

Our Services

A model this historic rewards operational candor, and Alfa Cytology runs Renca with its benchmark data worn openly: STR-validated banks, validated subcutaneous and intrarenal formats with the 2 × 105 orthotopic methodology, serial micro-CT and bioluminescence monitoring, and endpoint pathology with cytokeratin-8/18 identification and checkpoint immunophenotyping — all under one accountable preclinical operation, with the PD-1-monotherapy caveat stated in every study design.

Workflow of Renca Syngeneic Model Construction

Construction follows the published orthotopic and flank methodologies: Renca cells (parental or luciferase-RFP engineered) are expanded under authenticated conditions, implanted beneath the renal capsule or subcutaneously into BALB/c mice, tracked by imaging, treated after standardization, and analyzed with renal and metastatic endpoints. The workflow comprises the following stages.

  1. Cell authentication and banking: Renca or reporter derivatives are STR-profiled against the validated reference (per the PLoS ONE 2019 mouse-cell-line standard), confirmed mycoplasma-negative, and expanded into low-passage working banks under ATCC-formulated RPMI-1640 conditions.
  2. Cell harvest and formulation: Healthy cultures are trypsinized, washed, counted and viability-checked, then resuspended at 2 × 105 cells in 0.1 mL (intrarenal) or 5 × 106 cells in 100 μL (subcutaneous) of HBSS or complete medium.
  3. Anesthesia and implantation: BALB/c mice are anesthetized with isoflurane (or ketamine/xylazine per legacy protocols); cells are injected beneath the left renal capsule through a small flank approach with needle retention to minimize backflow, or implanted subcutaneously into the flank.
  4. Establishment monitoring and randomization: Luciferase arms are imaged after D-luciferin administration from early timepoints; kidney and lung signals are quantified serially; animals are randomized at protocol-specified baselines balancing primary and metastatic burden.
  5. Treatment administration: Experimental arms — TKIs (sunitinib, cabozantinib-class), checkpoint inhibitors alone and in combination, vascular-disruption agents, oncolytic viruses, and IL-2-era cellular products — proceed per study design with body-weight and toxicity monitoring.
  6. Imaging and interim measurements: Serial in vivo bioluminescence tracks primary and lung kinetics; micro-CT sessions quantify renal mass and osteolytic change on the orthotopic format; interim blood draws profile circulating leukocytes where immune-context arms are designed.
  7. Endpoint and histopathological analysis: Endpoints integrate tumor-bearing kidney wet weight, lung-metastatic counts by India-ink inflation and histology, imaging kinetics, and survival with histopathology (H&E plus cytokeratin-8/18 tumor identification, Ki67, CD8, PD-L1, and CA-IX immunohistochemistry) and terminal immune-context profiling.

Fig 3: Workflow for the establishment of Renca Syngeneic Models.Fig 2. Renca Syngeneic Model construction workflow.

Case Study-Renca Syngeneic Model Development

Alfa Cytology has conducted preclinical programs on the Renca platform spanning TKI-plus-checkpoint combination evaluation, vascular-disruption agent screening, and orthotopic metastatic-burden tracking with luciferase-RFP engineering. In these studies, implanted Renca tumors were monitored through scheduled imaging and caliper measurements, treated per randomized regimens, and characterized at endpoint by histopathology with cytokeratin-8/18 identification and checkpoint immunophenotyping. Study-level datasets are available upon request.

Fig 4: Case Study-Renca Syngeneic Model Development.

Why Choose Alfa Cytology?

Alfa Cytology pairs historic-line stewardship with combination-therapy benchmarking discipline, so every Renca study is executed with validated orthotopic technique, published survival benchmarks as design references, and reporting that states the model’s checkpoint caveats plainly.

  • Focused experience with Renca in subcutaneous and intrarenal orthotopic formats, including the 2 × 105 Renca-GL methodology and luciferase-RFP tracking.
  • A single coordinated team managing cell banking, renal surgery, in vivo imaging and micro-CT, and endpoint pathology under one quality framework.
  • Design fluency with TKI-plus-checkpoint combinations against the published 28/34/34/49-day survival benchmark, with the PD-1-monotherapy caveat stated upfront.
  • Endpoint panels pairing cytokeratin-8/18 tumor identification with CD8/PD-L1/CA-IX immunohistochemistry and India-ink lung-inflation metastatic enumeration.
  • Transparent milestone reporting and rapid scientific feedback throughout the engagement.

Contact Us

If your renal cancer program needs the field’s most venerable syngeneic RCC platform — with spontaneous lung and liver metastasis, published combination benchmarks, and orthotopic imaging capability — Alfa Cytology is ready to build the study around your hypothesis. Reach out to us with your regimen and endpoint requirements, or contact us today for a customized proposal and quotation for the Renca syngeneic model service.

Reference

  1. Liang, Zhihuang, et al. "Protocol for constructing an orthotopic mouse model of metastatic renal cell carcinoma." STAR protocols 7.2 (2026).

For research use only. Not intended for any clinical use.

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