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Antibody-dependent cellular cytotoxicity against drug-induced antigens in L5178Y mouse lymphoma
Abstract:
In vivo treatment with antineoplastic compounds has been reported to lead to the expression of new antigenic specificities which were not detected on parental cells, and which were transmissible as a genetic character. The current study is concerned with antibody-dependent cellular cytotoxic (ADCC) activity in serum of syngeneic mice challenged with LY/DTIC cells, a subline of LY murine lymphoma, antigenically altered by the drug DTIC. LY/DTIC target cells coated with LY/DTIC-immune serum were specifically lysed by virgin lymphocytes. The genetic background of the effector cells, whether syngeneic, allogeneic or xenogeneic, did not produce significant differences in the percentage of target-cell lysis. ADCC activity was reduced when the immune serum was added directly to the incubation medium, without precoating. Although sera from individual animals exhibited different levels of ADCC activity, they nevertheless followed the general trend of the pooled sera. Peak activity of ADCC was obtained in the sera collected on Days 8 and 30 after LY/DTIC cell challenge. The ADCC activity elicited by LY/DTIC cells may contribute to the rejection of drug-altered tumour cells.
Insights
Drug-altered tumor cells can trigger an immune response. This study shows that antibody-dependent cellular cytotoxicity (ADCC) in mice serum effectively targets these altered cancer cells, potentially aiding tumor rejection.
Area of Science:
- Immunology
- Cancer Research
- Pharmacology
Background:
- Antineoplastic agents can induce new antigens on tumor cells.
- These drug-induced antigens are heritable traits of the altered tumor cells.
- Antibody-dependent cellular cytotoxicity (ADCC) plays a role in immune surveillance.
Purpose of the Study:
- To investigate the antibody-dependent cellular cytotoxic (ADCC) activity in mice serum against drug-altered lymphoma cells.
- To determine the impact of genetic background on effector cells in ADCC.
- To identify the optimal time frame for observing peak ADCC activity post-challenge.
Main Methods:
- Induction of LY/DTIC cells (drug-altered murine lymphoma) in syngeneic mice.
- Measurement of ADCC activity using LY/DTIC target cells and syngeneic, allogeneic, or xenogeneic effector lymphocytes.
- Analysis of ADCC levels in serum collected at various time points after tumor cell challenge.
Main Results:
- Virgin lymphocytes effectively lysed LY/DTIC target cells coated with LY/DTIC-immune serum.
- The genetic background of effector cells did not significantly affect target cell lysis.
- ADCC activity was diminished when immune serum was added directly to incubation without pre-coating.
- Peak ADCC activity was observed in sera collected 8 and 30 days post-challenge.
Conclusions:
- ADCC activity elicited by drug-altered tumor cells may contribute to the rejection of these cells.
- The study highlights the potential of ADCC in anti-cancer immunity against neoantigen-expressing tumors.
- Timing of immune response is crucial for effective ADCC against altered tumor cells.