Like many other therapeutics, gene therapy can be very useful in areas where traditional approaches have fallen short. It has the potential to shift the paradigm around the treatment of some of the toughest tumors. So too, at Protheragen do we provide services for the development of cancer gene therapy through the entire therapeutic continuum—discovery in the laboratory through preclinical translation.
Overview of Cancer Gene Therapy
Cancer develops when healthy cells change genetically and begin to grow and spread uncontrollably. Changes in normal cells damage important functions such as the regulation of the cell cycle, apoptosis (programmed cell death), and repair of DNA, which enables cells to become both invasive and immortal. The complexity and variability of cancer, as well as the individual differences among patients, have made treating it with conventional therapies like chemotherapy, radiation, and surgery clinically ineffective. In addition, these therapies are often accompanied by severe side effects and are unlikely to reach the cancer cells, particularly in later stages of the disease.
Fig.1 The history of gene therapy. (Li X.,
et al., 2023)
Gene therapy can directly target the genetic basis of cancer and, therefore, may provide a potential solution. It can either correct genetic alterations, strengthen the immune response, or add therapeutic genes that specifically act on cancer cells by changing the genetic material of a patient's cells. This strategy is paving the way toward the creation of new, precise oncological therapies that are expected to have fewer toxic side effects and provide more enduring responses.
The Core Mechanisms of Cancer Gene Therapy
Cancer gene therapy revolves around modifying the genetic structure of cells in order to fix or change functions that lead to cancerous growths. Several mechanisms are employed, each suffering from a different cancer biology problem:
Gene Editing to Correct Mutations
One of the most hopeful approaches to gene therapy is the accurate alteration of mutations that lead to cancer with
CRISPR-Cas9 technology. This method of gene modification permits researchers to cleave DNA at designated sites, modifying damaging sequences or making advantageous changes. For instance, CRISPR is capable of correcting mutations in tumor suppressor genes, one of which is p53, a gene that is vital in hindering the unregulated cell division associated with cancer. By restoring these genes’ lost functions, researchers may prevent cancer cells from multiplying and enable the body’s natural defenses to take control.
Immune Modulation Through Gene Therapy
An additional strategy for cancer gene therapy is to focus on altering the immune system to more efficiently identify and combat neoplasm cells. One of the most prominent examples of this strategy is Chimeric Antigen Receptor T-cell therapy, or CAR-T. In
CAR-T therapy, T cells are custom from the patient and they will be modified genetically to contain a receptor which will bind to a specific protein expressed on the cancer cell membranes. After administration back to the patient, these custom T cells will find cancer cells and eliminate them with unmatched accuracy.
CAR-T has transformative therapeutic implications for leukemia and lymphoma. Selective infection of neoplastic cells is being achieved with genetically modified oncolytic viruses, which spare normal tissues. These selectively modified viruses eliminate neoplastic cells by carrying therapeutically relevant genes, which also elicit an immune response against the remaining malignant cells.
Gene Silencing to Inhibit Cancer Growth
Cancer gene therapy also focuses on gene silencing. Scientists are able to inhibit the expression of particular genes active within the cancer cells using techniques like
RNA interference (RNAi). For example, some cancers result from the overexpression of specific oncogenes, which are genes responsible for stimulating cell growth and proliferation, as well as cell survival. Gene therapy can effectively "turn off" signals driving cancer growth by silencing such genes. siRNA (small interfering RNA) molecules are designed specifically to target these oncogenes, thus allowing control of cancer on a genetic level.
Development of Cancer Gene Therapy
The upcoming prospects of cancer gene therapy are very positive. Advanced cancer treatments such as base editing and prime editing are likely to evolve with time, offering more precise and efficient changes to the genome. Unlike previous gene-editing technologies, which had far greater limitations, next-generation tools seem to be much more effective as they are designed to work with lower off-target effects and improve the precision of change.
In addition, overcoming the challenges that have restricted the effectiveness of gene therapy in the past is becoming easier due to advancements in nanotechnology, which is enhancing the ability to deliver genetic material to tumors. The delivery efficiency of nanoparticles can be tailored to specific cells and tissues, which also minimizes potential side effects.
Table 1. Gene therapy products approved for cancer therapeutic use. (Belete T. M., et al., 2021)
| Trade Name (Proper Name) |
Date of Approval and Approving Agency |
Vector and Modified Gene |
Indication |
Route of Administration |
| Gendicine |
2003 State Food and Drug Administration of China |
Adenoviral vector P53 |
Head and neck squamous cell carcinoma |
In vivo |
| Oncorine (Recombinant Human Adenovirus Type 5 Injection) |
2005 State Food and Drug Administration of China |
Adenovirus Type 5 |
Head and neck and esophagus cancer, Nasopharyngeal cancer, etc. |
In vivo |
| KymriahTM (tisagenlecleucel) |
August 2017 FDA |
CD19-specific CAR T Lentiviral vector |
Acute lymphoblastic leukaemia |
Ex vivo |
| YescartaTM (axicabtagene ciloleucel) |
October 2017 FDA |
CD19-specific CAR T Y-Retroviral vector |
Non-Hodgkin lymphoma |
Ex vivo |
| Imlygic (talimogene laherparepvec, T-Vec) |
2015 FDA |
GM-CSF HSV-1 |
Melanoma |
In vivo |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen focuses on the development of cancer gene therapy by integrating innovative approaches with multi-faceted services. We strive to advance the development of safe and effective gene therapies for cancer therapeutics by combining sophisticated technologies and specialized fields.
Workflow of Cancer Gene Therapy Development
Target Validation and Feasibility Assessment
We begin with comprehensive bioinformatics analysis, utilizing transcriptomic and mutational databases (e.g., TCGA, COSMIC) to pinpoint actionable cancer gene targets. Candidate validation includes CRISPR knockout/knock-in screens, qPCR profiling, and Western blot confirmation in relevant tumor models.
Vector Engineering and Optimization
Protheragen designs high-efficiency delivery platforms tailored to the target cancer type. AAVs are chosen for low-immunogenic, sustained expression in solid tumors; lentiviruses for stable integration in dividing cells; and lipid nanoparticles for transient, systemic delivery of nucleic acids. Capsid engineering, promoter tuning, and cargo optimization are integral parts of this stage.
In Vitro Assay Development
Custom cell-based assays are developed to evaluate therapeutic efficacy. These include viability assays (MTT, CellTiter-Glo), apoptosis detection (Annexin V/PI), invasion/migration (Transwell), and tumor sphere formation to test stem-like properties.
In Vivo Studies
Murine xenograft and syngeneic models are utilized to assess anti-tumor activity, safety, and pharmacokinetics. Biodistribution is measured via qPCR and in vivo imaging (bioluminescence, fluorescence), while immune responses are monitored through flow cytometry and ELISA.
Types of Cancer Gene Therapy Development
Cancer Animal Models for Gene Therapy Development
| Cancer Type |
Cell lines |
| CDX Models (Cell-Derived Xenograft Models) |
| Brain Cancer |
U-87 MG, LN-229, U-251 MG |
| Breast Cancer |
BT474, HCC1569, HCC1954, HCC70, JIMT-1 |
| Colon Cancer |
COLO 205, DLD-1, HCT-116, HCT-15, HT-29 |
| Gastric Cancer |
Hs 746T, NCI-N87, SNU-16, MKN-45 |
| Leukemia |
CCRF-CEM, HEL, HL-60, K-562, MV-4-11 |
| Liver Cancer |
Hep G2, HuH-7 |
| Renal Cancer |
786-O, OS-RC-2, A498, ACHN |
| Lung Cancer |
A549, Calu-1, Calu-3, Calu-6, HCC827 |
| Lymphoma |
SU-DHL-4, DB, Mino, Daudi, JeKo-1, Raji |
| Myeloma |
MM.1S, NCI-H929, RPMI-8226, OPM-2 |
| Ovary Cancer |
A2780, OVCAR-3, SK-OV-3 |
| Pancreatic Cancer |
AsPC-1, BxPC-3, Capan, CFPAC-1 |
| Syngeneic Mouse Models |
| Breast Cancer |
4T1, EMT6, JC, EO771 |
| Colon Cancer |
CT26.WT, MC-38, Colon26 |
| Leukemia |
C1498, L1210, WEHI-3 |
| Lung Cancer |
LLC1, KLN205 |
| Lymphoma |
A20, EL4, L5178-R, E.G7-OVA |
| Melanoma |
B16-F10, Clone-M3 |
| Humanized Immune System Mouse Models |
| Breast Cancer |
HCC1954, MDA-MB-231, JIMT-1 |
| Colon Cancer |
HT29, LoVo, Ls174T, HT-15 |
| Gastric Cancer |
NCI-N87, NUGC-4 |
| Lung Cancer |
HCC827, NCI-H1975, NCI-H292 |
| Lymphoma |
Raji, TMD8, MOLM-13 |
| Myeloma |
RPMI-8226, NCI-H929, MM.1S |
Protheragen is committed to advancing the frontier of cancer gene therapy through scientific excellence, technological innovation, and integrated service delivery. With the increasing complexity of oncology and the promise of precision medicine, our cancer gene therapy development services are designed to bring next-generation therapies from concept to clinic efficiently, safely, and effectively. Through partnerships rooted in expertise and a passion for impact, Protheragen is helping shape the future of cancer treatment—one gene at a time. If you are interested in our services, please feel free to
contact us.
References
- Li, Xuedan, et al. "Viral vector-based gene therapy." International journal of molecular sciences 24.9 (2023): 7736.
- Belete, Tafere Mulaw. "The current status of gene therapy for the treatment of cancer." Biologics: Targets and Therapy (2021): 67-77.
- Bulaklak, Karen, and Charles A. Gersbach. "The once and future gene therapy." Nature communications 11.1 (2020): 1-4.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
