AQA A-Level Biology Paper 1, November 2021: Question 7

10 marks · Medium difficulty · Short Answer

Explain the action and side effects of antibody-drug conjugates (ADCs) in cancer treatment, calculate an injection dosage, and evaluate drug testing methodology.

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Question

Question text

07.1 ADCs are molecules made of a monoclonal antibody linked to a cancer drug.

Figure 8 shows how an ADC enters and kills a tumour cell.

The process of entering the cell and the breakdown of the antibody to release the

drug is very similar to phagocytosis.

Figure 8

Use your knowledge of phagocytosis to describe how an ADC enters and kills the

tumour cell.

[3 marks]

07.2 Some of the antigens found on the surface of tumour cells are also found on the

surface of healthy human cells.

Use this information to explain why treatment with an ADC often causes side effects.

[2 marks]

Scientists investigated whether one type of ADC could be used to treat human breast

cancer.

This ADC is a monoclonal antibody combined with a drug to inhibit mitosis. The

monoclonal antibody binds to a protein found on human breast cancer cells.

The scientists placed small pieces of human breast cancer tissue under the skin of

mice.

The scientists then randomly divided the mice into three groups. They treated the

groups as follows on day 0.

Group G – control

Group H – injected with monoclonal antibody only

Group J – injected with ADC (monoclonal antibody + drug).

Every few days, the scientists measured the volume of the tumours formed from the

human breast cancer tissue.

Figure 9 shows the scientists’ results.

Figure 9

This source has been removed due to third-party copyright restrictions.

07.3 Mice in Group H were injected with 2 mg kg–1 of monoclonal antibody.

The monoclonal antibody was in a solution of concentration 500 mg dm–3

Calculate the volume of antibody solution that the scientists would have injected into a

23 g mouse. Give your answer in dm3 and in standard form.

[2 marks]

*21* dm3

07.4 Suggest one reason why there are no data for Group G and Group H after day 8

[1 mark]

07.5 Suggest and explain two further investigations that should be done before this ADC

is tested on human breast cancer patients.

[2 marks]

*22* 1

Mark scheme

Show the mark scheme

Question Marking Guidance Mark Comments

07.1 1. Cell ingests/engulfs the antibody/ADC 1. Accept endocytosis

for ingest/engulf

Cell membrane surrounds the antibody/ADC (to

take it inside the cell);

2. Lysosomes fuse with vesicle/phagosome

(containing ADC); 3. Accept hydrolytic

3. Lysozymes breakdown/digest the antibody/ADC enzyme for

to release the drug; lysozyme

07.2 1. ADC will bind to non-tumour/healthy cells; 1. Reject reference to

active site

2. Cause death/damage of non-tumour/healthy

cells

Cause damage to other organs/systems;

07.3 ‒5

Correct answer for 2 marks, 9.2 x 10 ;;

Accept for 1 mark,

0.046 (correct mass injected into 23g mouse)

0.000092 (correct answer but not in standard form)

07.4 Mice died

OR 1

– A-LEVEL BIOLOGY – –

Not ethical to continue;

07.5 1. Tested on other mammals to check for 1. Accept named

safety/side effects; mammal, eg rat

2. Tested on (healthy) humans to check for 2. Accept: Tested on

14 safety/side effects; (healthy) human

2 max tissue/cells to check

3. See if repeat doses stop the tumours regrowing for no side-effects

(in Group J);

4. Investigate different concentrations of ADC to

find suitable/safe dosage;

How to answer it

Monoclonal Antibodies: Antibody-Drug Conjugates (ADCs) in Cancer Therapy

📋 What This Question Tests

This question assesses your ability to apply core biological mechanisms to novel medical contexts. Specifically, it tests:

Application of phagocytosis: Explaining endocytosis, phagosome formation, lysosomal fusion, and enzymatic breakdown in the context of targeted drug delivery.
Specificity and side effects: Linking antigen presentation on healthy cells to off-target cytotoxicity.
Drug calculation & unit conversion: Multi-step unit conversions (g to kg, mg to volume) and expressing final values in standard form.
Practical experimental design & drug trials: Understanding ethical termination of animal experiments and the pre-clinical/clinical trial pipeline for novel pharmaceuticals.

Part 07.1 (3 Marks)

Phagocytosis Mechanism Applied to ADC Entry & Breakdown

Using phagocytosis knowledge to explain how an ADC enters and destroys a tumour cell

✅ Mark Scheme Points

Entry: Cell invaginates / membrane surrounds / ingests / engulfs the ADC via endocytosis [1 mark].
Fusion: Lysosomes fuse with the vesicle / phagosome containing the ADC [1 mark].
Digestion: Lysozymes (or hydrolytic enzymes) digest / hydrolyse the antibody to release the drug [1 mark].

💡 Key Knowledge

Endocytosis: The plasma membrane invaginates around the bound ADC, pinching off to form an intracellular vesicle (phagosome).
Lysosome vs Lysozyme: A lysosome is the membrane-bound organelle; lysozymes / hydrolytic enzymes are the catalytic proteins inside it.
Drug Action: The antibody serves purely as a delivery vehicle; breaking peptide bonds releases the cytotoxic molecule inside the cytoplasm to trigger apoptosis.

🧠 Exam Technique

The question states: "The process... is very similar to phagocytosis." Always mirror the standard 3-step phagocytosis narrative:

Engulfment into vesicle → Lysosome fusion → Hydrolytic enzyme digestion

❌ Common Errors

Confusing lysosome (organelle) and lysozyme (enzyme). You must use both terms in their correct context to secure all 3 marks.
Stating that the drug is "absorbed" through the membrane without mentioning engulfment or vesicle formation.

Total: 3 Marks (1 mark per distinct sequential stage)

Part 07.2 (2 Marks)

Explaining Side Effects of ADC Therapy

Linking non-tumour antigen presentation to tissue damage

✅ Mark Scheme Points

ADC binds to healthy / non-tumour cells [1 mark].
Causes death / damage of healthy cells OR causes damage to other organs/systems [1 mark].

❌ Common Errors & Disqualifications

Crucial Mark Scheme Reject: Never say the ADC binds to the "active site" of healthy cells. Antibodies have antigen-binding sites, not active sites (enzymes have active sites).
Vague statements like "it harms the body" without specifying that healthy cells are killed or damaged.

Total: 2 Marks (1 mark for binding to normal cells, 1 mark for cytotoxic effect on them)

Part 07.3 (2 Marks)

Dosage & Volume Calculation

Calculate volume of 500 mg dm⁻³ antibody solution injected into a 23 g mouse (dose = 2 mg kg⁻¹)

📐 Step-by-Step Calculation

Convert the mouse's mass from grams (g) to kilograms (kg):
Mass in kg = 23 g ÷ 1000 = 0.023 kg
Calculate the total mass of antibody required (in mg):
Dose required is 2 mg per 1 kg of body mass:
Mass of antibody = 0.023 kg × 2 mg kg⁻¹ = 0.046 mg
(Award 1 mark if this value is found correctly)
Calculate the volume of solution required (in dm³):
Volume (dm³) = Mass (mg) ÷ Concentration (mg dm⁻³)
Volume = 0.046 mg ÷ 500 mg dm⁻³ = 0.000092 dm³
Convert the final answer into standard form:
Move the decimal point 5 places to the right:
9.2 × 10⁻⁵ dm³

🧠 Unit Check

Notice the units given in the question stem:

Dose: mg kg⁻¹
Concentration: mg dm⁻³
Mouse mass: g → must convert to kg !

Since concentration uses mg , leaving the drug mass in mg allows direct division to get dm³ .

❌ Calculation Traps

Forgetting to convert 23 g into kg (yields 0.092 dm³ → 0 marks).
Writing 0.000092 dm³ without converting to standard form (only gives 1 mark).
Incorrect exponent sign (e.g. writing 9.2 × 10⁵ instead of 9.2 × 10⁻⁵).

Correct Answer: 9.2 × 10⁻⁵ dm³ [2 marks]
Partial credit (1 mark): 0.046 mg calculated OR 0.000092 given without standard form.

Part 07.4 (1 Mark)

Interpreting Missing Experimental Data

Suggest why there are no data for Group G (control) and Group H (monoclonal antibody only) after day 8

✅ Acceptable Answers (Either one)

The mice died [1 mark].
It was not ethical to continue (e.g. tumours grew too large / caused too much distress, so mice were euthanised) [1 mark].

🧠 Experimental Reasoning

Groups G (control) and H (monoclonal antibody without the cytotoxic drug) did not receive effective anti-cancer therapy. In animal cancer studies, if tumour burden exceeds permitted ethical limits or causes suffering/death, the study protocol terminates for those groups.

Total: 1 Mark

Part 07.5 (2 Marks)

Pre-Clinical & Clinical Trial Next Steps

Suggest and explain two further investigations before testing on human breast cancer patients

✅ Any TWO of the following (1 mark each):

Test on other non-human mammals: To check for safety, toxicity, or side effects in a whole living system.
Test on healthy human volunteers: To check for safety, unexpected side effects, or immune reactions.
Test different concentrations / dosages: To determine the optimum therapeutic dose with minimal toxicity (suitable/safe dosage).
Investigate repeat / regular doses (on Group J): To see if repeat administration stops tumours from regrowing long-term.

🧠 Exam Technique: "Suggest and Explain"

Make sure your answer pairs an action with a clear purpose:

Action: Test on other mammals / healthy humans...
Purpose: ...to check for side effects / safety.

Note: Testing directly on breast cancer patients cannot be credited, as the prompt specifically asks what must be done before testing on patients!

Total: 2 Marks (max 2)

Topics

Biology · Practical skills · 3.2 Cells · Experimental design · Data analysis

Question and mark scheme from the AQA A-Level Biology examination, Paper 1, November 2021. QuestionVault is an independent revision resource; questions remain the copyright of the awarding body.